NM_006768.5:c.723A>G

Variant names:

• chr12-111672685-T-C
• rs3782886
• NM_006768.5:c.723A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006768.5(BRAP):​c.723A>G​(p.Arg241Arg) 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
• Publications: 95 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006768.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRAP	NM_006768.5	MANE Select	c.723A>G	p.Arg241Arg	synonymous	Exon 5 of 12	NP_006759.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRAP	ENST00000419234.9	TSL:1 MANE Select	c.723A>G	p.Arg241Arg	synonymous	Exon 5 of 12	ENSP00000403524.3	Q7Z569-1
	BRAP	ENST00000327551.6	TSL:1	c.633A>G	p.Arg211Arg	synonymous	Exon 5 of 12	ENSP00000330813.5	J3KNN7
	BRAP	ENST00000871570.1		c.684A>G	p.Arg228Arg	synonymous	Exon 4 of 11	ENSP00000541629.1

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

GnomAD2 exomes AF: 0.0193 AC: 4851 AN: 251256 AF XY: 0.0180

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 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

African (AFR) AF: 0.0000299 AC: 1 AN: 33474

American (AMR) AF: 0.000336 AC: 15 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.000459 AC: 12 AN: 26132

East Asian (EAS) AF: 0.258 AC: 10243 AN: 39688

South Asian (SAS) AF: 0.000220 AC: 19 AN: 86226

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53320

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000369 AC: 41 AN: 1111868

Other (OTH) AF: 0.00600 AC: 362 AN: 60380

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

African (AFR) AF: 0.00 AC: 0 AN: 41582

American (AMR) AF: 0.000850 AC: 13 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.231 AC: 1195 AN: 5184

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4822

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68032

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.00595 Hom.: 456

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	13
DANN	Benign	0.74
PhyloP100		0.24
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

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