12-111659253-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_006768.5(BRAP):c.1065G>A(p.Thr355=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00298 in 1,614,114 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (10 hom.)
• Consequence: BRAP NM_006768.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.23

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 12-111659253-C-T is Benign according to our data. Variant chr12-111659253-C-T is described in ClinVar as [Benign]. Clinvar id is 781699.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-5.23 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRAP	NM_006768.5	c.1065G>A	p.Thr355=	synonymous_variant	8/12	ENST00000419234.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRAP	ENST00000419234.9	c.1065G>A	p.Thr355=	synonymous_variant	8/12	1	NM_006768.5	P1
BRAP	ENST00000327551.6	c.975G>A	p.Thr325=	synonymous_variant	8/12	1
BRAP	ENST00000547043.1	n.969G>A		non_coding_transcript_exon_variant	4/8	3

Frequencies

GnomAD3 genomes AF: 0.00238 AC: 362 AN: 152168 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000918

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00575

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00369

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00242 AC: 607 AN: 251338 Hom.: 0 AF XY: 0.00237 AC XY: 322 AN XY: 135822

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.00153

Gnomad ASJ exome AF: 0.000893

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00101

Gnomad FIN exome AF: 0.00481

Gnomad NFE exome AF: 0.00339

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00305 AC: 4456 AN: 1461828 Hom.: 10 Cov.: 31 AF XY: 0.00302 AC XY: 2194 AN XY: 727218

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.00143

Gnomad4 ASJ exome AF: 0.000689

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00105

Gnomad4 FIN exome AF: 0.00500

Gnomad4 NFE exome AF: 0.00341

Gnomad4 OTH exome AF: 0.00343

GnomAD4 genome AF: 0.00238 AC: 362 AN: 152286 Hom.: 0 Cov.: 32 AF XY: 0.00223 AC XY: 166 AN XY: 74454

Gnomad4 AFR AF: 0.000505

Gnomad4 AMR AF: 0.000917

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00575

Gnomad4 NFE AF: 0.00369

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00304 Hom.: 1

Bravo AF: 0.00212

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.00349

EpiControl AF: 0.00326

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 13, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	0.40
Dann	Benign	0.77

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: rs151101195; hg19: chr12-112097057;