12-111685480-A-G

Position:

• chr12-111685480-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.79).
• 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/exons	MANE	Protein	UniProt
BRAP	NM_006768.5	c.82+231T>C		intron_variant		ENST00000419234.9	NP_006759.3
BRAP	XM_005253944.5	c.205+108T>C		intron_variant			XP_005254001.1
BRAP	XM_017019992.2	c.82+231T>C		intron_variant			XP_016875481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRAP	ENST00000419234.9	c.82+231T>C		intron_variant		1	NM_006768.5	ENSP00000403524.3
BRAP	ENST00000327551.6	c.-9+108T>C		intron_variant		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

Gnomad4 AFR exome AF: 0.800

Gnomad4 AMR exome AF: 0.427

Gnomad4 ASJ exome AF: 0.171

Gnomad4 EAS exome AF: 0.936

Gnomad4 SAS exome AF: 0.582

Gnomad4 FIN exome AF: 0.256

Gnomad4 NFE exome AF: 0.275

Gnomad4 OTH exome AF: 0.367

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

Gnomad4 AFR AF: 0.782

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.944

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.436

Alfa AF: 0.310 Hom.: 11963

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs601663; hg19: chr12-112123284;