chr12-111675854-C-T

Variant names:

• chr12-111675854-C-T
• rs7136874
• NM_006768.5:c.634-3080G>A

Variant summary

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

The NM_006768.5(BRAP):​c.634-3080G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 151,756 control chromosomes in the GnomAD database, including 14,286 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 0.36 (14286 hom., cov: 30)
• Consequence: BRAP NM_006768.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.679
• Publications: 13 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRAP	NM_006768.5	c.634-3080G>A		intron_variant	Intron 4 of 11	ENST00000419234.9	NP_006759.3
BRAP	XM_005253944.5	c.757-3080G>A		intron_variant	Intron 4 of 11		XP_005254001.1
BRAP	XM_017019992.2	c.472-3080G>A		intron_variant	Intron 3 of 10		XP_016875481.1
BRAP	XM_047429622.1	c.187-3080G>A		intron_variant	Intron 2 of 9		XP_047285578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRAP	ENST00000419234.9	c.634-3080G>A		intron_variant	Intron 4 of 11	1	NM_006768.5	ENSP00000403524.3
BRAP	ENST00000327551.6	c.544-3080G>A		intron_variant	Intron 4 of 11	1		ENSP00000330813.5

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54337 AN: 151638 Hom.: 14247 Cov.: 30

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.338

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.359 AC: 54439 AN: 151756 Hom.: 14286 Cov.: 30 AF XY: 0.359 AC XY: 26648 AN XY: 74140

African (AFR) AF: 0.682 AC: 28189 AN: 41324

American (AMR) AF: 0.330 AC: 5011 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 374 AN: 3466

East Asian (EAS) AF: 0.898 AC: 4643 AN: 5168

South Asian (SAS) AF: 0.332 AC: 1595 AN: 4804

European-Finnish (FIN) AF: 0.167 AC: 1756 AN: 10540

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11934 AN: 67940

Other (OTH) AF: 0.335 AC: 705 AN: 2104

Alfa AF: 0.289 Hom.: 2034

Bravo AF: 0.392

Asia WGS AF: 0.553 AC: 1923 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.17
DANN	Benign	0.57
PhyloP100		-0.68
Mutation Taster		=100/0	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: rs7136874; hg19: chr12-112113658;