12-111685480-A-G

Variant names:

• chr12-111685480-A-G
• rs601663
• NM_006768.5:c.82+231T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006768.5(BRAP):​c.82+231T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 1,010,210 control chromosomes in the GnomAD database, including 74,245 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 0.46 (20561 hom., cov: 32)
  • Exomes 𝑓: 0.32 (53684 hom.)
• Consequence: BRAP NM_006768.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600
• Publications: 24 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRAP	NM_006768.5	c.82+231T>C		intron_variant	Intron 1 of 11	ENST00000419234.9	NP_006759.3
BRAP	XM_005253944.5	c.205+108T>C		intron_variant	Intron 1 of 11		XP_005254001.1
BRAP	XM_017019992.2	c.82+231T>C		intron_variant	Intron 1 of 10		XP_016875481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRAP	ENST00000419234.9	c.82+231T>C		intron_variant	Intron 1 of 11	1	NM_006768.5	ENSP00000403524.3
BRAP	ENST00000327551.6	c.-9+108T>C		intron_variant	Intron 1 of 11	1		ENSP00000330813.5

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69850 AN: 151992 Hom.: 20507 Cov.: 32

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.944

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.437

GnomAD4 exome AF: 0.320 AC: 274265 AN: 858100 Hom.: 53684 AF XY: 0.322 AC XY: 133951 AN XY: 415544

African (AFR) AF: 0.800 AC: 14101 AN: 17618

American (AMR) AF: 0.427 AC: 4416 AN: 10352

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 2149 AN: 12596

East Asian (EAS) AF: 0.936 AC: 21698 AN: 23188

South Asian (SAS) AF: 0.582 AC: 19629 AN: 33736

European-Finnish (FIN) AF: 0.256 AC: 5533 AN: 21584

Middle Eastern (MID) AF: 0.422 AC: 1002 AN: 2376

European-Non Finnish (NFE) AF: 0.275 AC: 192547 AN: 700670

Other (OTH) AF: 0.367 AC: 13190 AN: 35980

GnomAD4 genome AF: 0.460 AC: 69970 AN: 152110 Hom.: 20561 Cov.: 32 AF XY: 0.464 AC XY: 34525 AN XY: 74380

African (AFR) AF: 0.782 AC: 32449 AN: 41510

American (AMR) AF: 0.433 AC: 6612 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 569 AN: 3470

East Asian (EAS) AF: 0.944 AC: 4861 AN: 5152

South Asian (SAS) AF: 0.604 AC: 2913 AN: 4820

European-Finnish (FIN) AF: 0.245 AC: 2597 AN: 10608

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18677 AN: 67958

Other (OTH) AF: 0.436 AC: 920 AN: 2112

Alfa AF: 0.323 Hom.: 18380

Bravo AF: 0.488

Asia WGS AF: 0.732 AC: 2544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.2
DANN	Benign	0.35
PhyloP100		-0.0060
PromoterAI		0.0096	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs601663; hg19: chr12-112123284;