rs11066001

Positions:

• chr12-111681367-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006768.5(BRAP):​c.443+270A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00785 in 151,164 control chromosomes in the GnomAD database, including 143 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 0.0078 (143 hom., cov: 31)
• Consequence: BRAP NM_006768.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRAP	NM_006768.5	c.443+270A>G		intron_variant		ENST00000419234.9	NP_006759.3
BRAP	XM_005253944.5	c.566+270A>G		intron_variant			XP_005254001.1
BRAP	XM_017019992.2	c.281+270A>G		intron_variant			XP_016875481.1
BRAP	XM_047429622.1	c.-5+1779A>G		intron_variant			XP_047285578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRAP	ENST00000419234.9	c.443+270A>G		intron_variant		1	NM_006768.5	ENSP00000403524	P1
BRAP	ENST00000327551.6	c.353+270A>G		intron_variant		1		ENSP00000330813

Frequencies

GnomAD3 genomes AF: 0.00787 AC: 1189 AN: 151050 Hom.: 143 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000856

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.000833

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00529

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

GnomAD4 genome AF: 0.00785 AC: 1186 AN: 151164 Hom.: 143 Cov.: 31 AF XY: 0.00905 AC XY: 668 AN XY: 73790

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000855

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.000833

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000148

Gnomad4 OTH AF: 0.00476

Alfa AF: 0.00217 Hom.: 1

Bravo AF: 0.00887

Asia WGS AF: 0.0290 AC: 101 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.4
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs11066001; hg19: chr12-112119171;