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LYFE SCIENCES
Project: HERA
NM_007294.3:c.301+7G>A
p.?  ·  BRCA1
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Classification rationale
1

The BRCA1 c.301+7G>A (NP_009225.1:p.?) variant has been reported in ClinVar and is classified there as Benign by the ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel.

clinvar ↗ cspec ↗
2

This variant is absent from gnomAD v2.1 but is present in gnomAD v4.1 at AF 5.40093e-05 (87/1610834 alleles; 0 homozygotes), so it is not absent from population controls.

gnomad_v2 ↗ gnomad_v4 ↗
3

Functional evidence supports a benign effect: ENIGMA BRCA1 Table 9 assigns BS3_Strong for this variant, and RNA studies reported no aberrant splicing.

PMID:22505045 ↗ PMID:24667779 ↗
4

Computational splicing evidence predicts possible splice impact, with a SpliceAI maximum delta score of 0.29, which meets the ENIGMA BRCA1 PP3 threshold and does not meet the BP4 threshold.

spliceai ↗ cspec ↗
Applied criteria
Met
Not met
Not assessed
N/A
Very strong
Strong
Moderate
Supporting
Pathogenic evidence
PVS
PVS1
PS
PS1
PS2
PS3
PS4
PM
PM1
PM2
PM3
PM4
PM5
PM6
PP
PP1
PP2
PP3
PP4
PP5
Benign evidence
BA
BA1
BS
BS1
BS2
BS3
BS4
BP
BP1
BP2
BP3
BP4
BP5
BP6
BP7
PVS1
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—
Rationale
Select a criterion to inspect its explanation.
Evidence used
  • —
Gaps remaining
  • —
Rule
—
Publications
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Research and evidence
gnomAD v2.1 evidence
v2.1
gnomAD v4.1 evidence
v4.1
01
Population
gnomAD v2.1Absent from gnomAD v2.1.
gnomAD v4.1This variant is present in gnomAD v4.1 (AF= 5.40093e-05; MAF= 0.00540%, 87/1610834 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.000135199; MAF= 0.01352%, 4/29586 alleles, homozygotes = 0); grpmax FAF= 5.311e-05.
gnomAD v2 ↗ gnomAD v4 ↗
ClinVar evidence
02
ClinVar
This variant has been reported in ClinVar as Benign (11 clinical laboratories) and as Likely benign (3 clinical laboratories) and as Uncertain significance (1 clinical laboratory) and as Benign by ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, ClinGen (expert panel).
ClinVar ↗
03
Functional
No functional summary recorded.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts possible splice impact for this variant (max delta score = 0.29).
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant has not previously been reported in somatic cancers (COSMIC).
COSMIC ↗
06
Cancer hotspots
No cancer hotspot summary recorded.