rs3782886

Positions:

• chr12-111672685-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006768.5(BRAP):​c.723A>G​(p.Arg241=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00739 in 1,613,886 control chromosomes in the GnomAD database, including 1,521 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0080 (148 hom., cov: 32)
  • Exomes 𝑓: 0.0073 (1373 hom.)
• Consequence: BRAP NM_006768.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244

Genes affected

BRAP (HGNC:1099): (BRCA1 associated protein) The protein encoded by this gene was identified by its ability to bind to the nuclear localization signal of BRCA1 and other proteins. It is a cytoplasmic protein which may regulate nuclear targeting by retaining proteins with a nuclear localization signal in the cytoplasm. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=0.244 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRAP	NM_006768.5	c.723A>G	p.Arg241=	synonymous_variant	5/12	ENST00000419234.9	NP_006759.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRAP	ENST00000419234.9	c.723A>G	p.Arg241=	synonymous_variant	5/12	1	NM_006768.5	ENSP00000403524	P1
BRAP	ENST00000327551.6	c.633A>G	p.Arg211=	synonymous_variant	5/12	1		ENSP00000330813
BRAP	ENST00000547043.1	n.627A>G		non_coding_transcript_exon_variant	1/8	3

Frequencies

GnomAD3 genomes AF: 0.00807 AC: 1228 AN: 152210 Hom.: 148 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00525

GnomAD3 exomes AF: 0.0193 AC: 4851 AN: 251256 Hom.: 662 AF XY: 0.0180 AC XY: 2441 AN XY: 135804

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000463

Gnomad ASJ exome AF: 0.000595

Gnomad EAS exome AF: 0.260

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00572

GnomAD4 exome AF: 0.00732 AC: 10696 AN: 1461558 Hom.: 1373 Cov.: 30 AF XY: 0.00725 AC XY: 5269 AN XY: 727076

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000336

Gnomad4 ASJ exome AF: 0.000459

Gnomad4 EAS exome AF: 0.258

Gnomad4 SAS exome AF: 0.000220

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.0000369

Gnomad4 OTH exome AF: 0.00600

GnomAD4 genome AF: 0.00804 AC: 1225 AN: 152328 Hom.: 148 Cov.: 32 AF XY: 0.00926 AC XY: 690 AN XY: 74474

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000850

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00624 Hom.: 228

Bravo AF: 0.00906

Asia WGS AF: 0.0330 AC: 114 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	13
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3782886; hg19: chr12-112110489; COSMIC: COSV59535903; COSMIC: COSV59535903;