NM_017745.5:c.519C>T is a synonymous variant (p.Ser173=) in exon 4 of BCOR that does not alter the protein sequence. SpliceAI predicts no impact on splicing (max delta score 0.00), consistent with BP7 (Supporting Benign).1 Three clinical laboratories in ClinVar classify this variant as Likely Benign, consistent with BP6 (Supporting Benign).2 The variant is observed in gnomAD at 0.035% in v4.1 (424 alleles) with no homozygotes, which is below the PM2 threshold of 0.1% but also below the BS1 threshold of 0.3%; population frequency is uninformative for this synonymous variant.3 No pathogenic or likely pathogenic ClinVar submissions, no functional evidence of damaging effect, and no segregation, de novo, or case-control data were identified to support a pathogenic classification.4
BCOR
Final classification
Likely Benign
BCOR c.519C>T · p.Ser173=
BCOR
NM_017745.5:c.519C>T is a synonymous variant (p.Ser173=) in exon 4 of BCOR that does not alter the protein sequence.
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: BP6 supporting benign, BP7 supporting benign; combination = 2 supporting benign, which maps to Likely Benign.
Classification rationale
BP6BP7
Likely Benign
BCOR c.519C>T
BP6 + BP7
→
Likely Benign
Gene diagram
· NM_017745.5 · variants mapped to exon structure
BCOR
NM_017745.5
Fetching transcript structure from UCSC…
Applied criteria · 2 met · select any tile
Met
Not met
Not assessed
N/A
Strength
very strong
supporting
Pathogenic evidence
PVS
PS
PM
PP
Benign evidence
BA
BS
BP
—
—
—
Rationale
Select a criterion.
Sources
Evidence used
Gaps remaining
Rule
—
Research & evidence
Population frequency · supports benign
gnomAD v4.1
gnomAD v2.1
v4.1
This variant is present in gnomAD v4.1 (AF= 0.000350447; MAF= 0.03504%, 424/1209884 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000430098; MAF= 0.04301%, 385/895144 alleles, homozygotes = 0); grpmax FAF= 0.00039444.
v2.1
This variant is present in gnomAD v2.1 (AF= 0.000165827; MAF= 0.01658%, 34/205033 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000281187; MAF= 0.02812%, 26/92465 alleles, homozygotes = 0); grpmax FAF= 0.00021222.
🇨🇦 CA
Not available in gnomAD-Canada v1.0.
Allele frequency by ancestry
three datasets · side by side
gnomAD v4.1
0.035%
· 424 / 1,209,884
0 hom · FAF 0.039%
0 hom · FAF 0.039%
European (non-Finnish) 385 / 895,144 |
0.043% |
Remaining individuals 17 / 47,603 |
0.036% |
South Asian 16 / 56,768 |
0.028% |
Admixed American 3 / 45,821 |
0.0065% |
African/African American 2 / 57,063 |
0.0035% |
East Asian 1 / 33,762 |
0.003% |
+ 4 not observed (European (Finnish), Amish, Middle Eastern, Ashkenazi Jewish)
gnomAD v2.1
0.017%
· 34 / 205,033
0 hom · FAF 0.021%
0 hom · FAF 0.021%
European (non-Finnish) 26 / 92,465 |
0.028% |
South Asian 4 / 19,080 |
0.021% |
Admixed American 3 / 28,048 |
0.011% |
East Asian 1 / 14,844 |
0.0067% |
+ 4 not observed (African/African American, Ashkenazi Jewish, European (Finnish), Remaining individuals)
gnomAD Canada 🇨🇦
Absent
· 0 / ?
0 hom
0 hom
Not observed in any ancestry group.
ClinVar
This variant is present in ClinVar (Variation ID: 210524); submission details unavailable.
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
Functional
Unknown Oncogenic Effect
OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
COSMIC
Cancer hotspots
Somatic evidence
Not in COSMIC / hotspots
COSMIC
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV60708452, n = 1 times).
Hotspots
This variant does not lie in a statistically significant hotspot.
Sources & reference links
Triaged references · 2 PMIDs not cited in assessment
25741868 ↗
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.
CLINVAR
28492532 ↗
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.
CLINVAR