Variant classification summary

NM_021946.4:c.1953C>T

BCORL1 · NP_068765.3:p.(His651=) · NM_021946.4

GRCh37: chrX:129148701 C>T · GRCh38: chrX:130014725 C>T

Gene: BCORL1 Transcript: NM_021946.4

Final call

VUS

BP7 supporting

Variant details

Gene

BCORL1

Transcript

NM_021946.4

Protein

NP_068765.3:p.(His651=)

gnomAD AF

2.47622003361056e-06 (v4.1)

ClinVar

OncoKB

Unknown Oncogenic Effect

Classification rationale

Interpretation summary

Generated evidence synthesis

1

BP7 (Supporting): synonymous change with no predicted splicing impact, SpliceAI maximum delta 0.001, far below the 0.2 flag threshold.

2

Overall classification VUS: a single supporting benign criterion does not reach the Likely Benign threshold under generic ACMG/AMP 2015 combination rules.

Final determination: 1 BP alone does not meet any generic ACMG combination threshold, so classification is Uncertain Significance.

Criteria assessment

ACMG/AMP criteria review

Criteria shown when status is available

All criteria require review: For research and educational purposes only.

Criterion	Status	Rationale	Evidence used
PVS1	N/A	Not applicable: the variant is synonymous (p.(His651=)) and cannot trigger nonsense-mediated decay or truncation, which PVS1 requires.	pvs1_generic_framework generic_acmg_combination_rules
PS1	N/A	Not applicable: a synonymous change produces no altered amino acid to compare with a previously established pathogenic variant.	generic_acmg_combination_rules
PS2	Not assessed	Not assessed: no parental testing or confirmed de novo occurrence data were available.
PS3	Not assessed	Not assessed: no functional or validated assay evidence was available for this variant.
PS4	Not assessed	Not assessed: no case-control cohort or variant-specific disease association data were available.
PM1	N/A	Not applicable: the synonymous change leaves the amino acid unchanged, so no residue can be evaluated for mutational hotspot or critical-domain membership.	generic_acmg_combination_rules
PM2	Not met	Not met: the variant is observed three times in gnomAD v4.1 (AF 2.5e-06), so it is not absent from population controls.	gnomad_v2 gnomad_v4 gnomad_canada
PM3	Not assessed	Not assessed: no second pathogenic allele or phase data showing the variant in trans with a disease-causing allele was available.	generic_acmg_combination_rules
PM4	N/A	Not applicable: a synonymous substitution causes no protein length change, leaving nothing for this criterion to evaluate.	pvs1_generic_framework generic_acmg_combination_rules
PM5	N/A	Not applicable: no missense change exists at this residue to compare with a previously pathogenic missense change at the same position.	generic_acmg_combination_rules
PM6	Not assessed	Not assessed: no unconfirmed de novo report or parental origin information was available.
PP1	Not assessed	Not assessed: no pedigree or segregation data across informative family members was documented.
PP2	N/A	Not applicable: no missense change is present, so the gene's missense-constraint properties are irrelevant here.	generic_acmg_combination_rules
PP3	N/A	Not applicable: missense predictors do not apply to a synonymous change; splice evidence is evaluated under BP7 instead.
PP4	Not assessed	Not assessed: no specific patient phenotype matching a BCORL1-associated disorder was documented.
PP5	Not met	Not met: the exact variant is absent from ClinVar, with no expert-panel Pathogenic or Likely pathogenic classification.	clinvar
BA1	Not met	Not met: gnomAD v4.1 AF of 2.5e-06 (3/1,211,524 alleles) is far below a common-variant frequency threshold.	gnomad_v4
BS1	Not met	Not met: the observed population frequency (AF 2.5e-06) does not exceed the maximum credible disease frequency.	gnomad_v4
BS2	Not assessed	Not assessed: no homozygotes or individual-level carrier health status was available to establish benignity in healthy adults.	gnomad_v4
BS3	Not assessed	Not assessed: no functional assay evidence showing normal or wild-type function was available.
BS4	Not assessed	Not assessed: no pedigree or non-segregation observations were documented.
BP1	N/A	Not applicable: no missense change is present to evaluate against the gene's truncating-variant disease mechanism.	generic_acmg_combination_rules
BP2	Not assessed	Not assessed: no phase or inheritance data showing the variant in cis or trans with another clinically classified allele was available.	generic_acmg_combination_rules
BP3	N/A	Not applicable: the synonymous change does not alter protein length in a repetitive region, leaving nothing to evaluate.	pvs1_generic_framework generic_acmg_combination_rules
BP4	N/A	Not applicable: missense predictors do not apply to a synonymous change; splice evidence is evaluated under BP7 instead.
BP5	Not assessed	Not assessed: no alternative molecular diagnosis or phenotype-explaining pathogenic variant was documented.
BP6	Not met	Not met: the exact variant is absent from ClinVar, with no expert-panel Benign or Likely benign classification.	clinvar
BP7	Met	Met (supporting): synonymous change with no predicted splicing impact, SpliceAI maximum delta 0.001, far below the 0.2 flag threshold.	spliceai

Disclaimer: The content and results provided by LYFE Sciences are for research and educational purposes only and must not be used as a substitute for professional medical judgment, diagnosis, or treatment. Always consult a qualified healthcare professional before making any clinical decisions.