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LYFE SCIENCES
Project: HERA
NM_032043.3:c.1474-3T>C
p.?  ·  BRIP1
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Classification rationale
1

The BRIP1 NM_032043.3:c.1474-3T>C (NP_114432.2:p.?) variant has been reported in ClinVar with predominantly benign and likely benign submissions, although uncertain significance submissions are also present.

clinvar ↗
2

This variant is present in population databases, including gnomAD v4.1 at an overall allele frequency of 0.01185% (191/1611312) and a highest observed South Asian frequency of 0.20440% (186/90996), with similar South Asian enrichment in gnomAD v2.1 at 0.16343% (50/30594); these values are above a 0.1% PM2 rarity threshold but below BA1 and BS1 thresholds.

gnomad_v2 ↗ gnomad_v4 ↗
3

In silico splice prediction does not support a significant splice effect, with a SpliceAI maximum delta score of 0.11, supporting BP4 and arguing against PP3.

spliceai ↗
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 v2.1This variant is present in gnomAD v2.1 (AF= 0.000207267; MAF= 0.02073%, 52/250884 alleles, homozygotes = 1) and has highest observed frequency in the South Asian population (AF= 0.00163431; MAF= 0.16343%, 50/30594 alleles, homozygotes = 1); grpmax FAF= 0.00127276.
gnomAD v4.1This variant is present in gnomAD v4.1 (AF= 0.000118537; MAF= 0.01185%, 191/1611312 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 0.00204405; MAF= 0.20440%, 186/90996 alleles, homozygotes = 0); grpmax FAF= 0.0018038.
gnomAD v2 ↗ gnomAD v4 ↗
ClinVar evidence
02
ClinVar
This variant has been reported in ClinVar as Likely benign (5 clinical laboratories) and as Benign (4 clinical laboratories) and as Uncertain significance (4 clinical laboratories).
ClinVar ↗
03
Functional
No functional summary recorded.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.11).
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.