12-111659253-C-T

Variant names:

• chr12-111659253-C-T
• rs151101195
• NM_006768.5:c.1065G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_006768.5(BRAP):​c.1065G>A​(p.Thr355Thr) 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
• Publications: 3 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 -11 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 VariationId is 781699.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-5.23 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 10 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006768.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRAP	NM_006768.5	MANE Select	c.1065G>A	p.Thr355Thr	synonymous	Exon 8 of 12	NP_006759.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRAP	ENST00000419234.9	TSL:1 MANE Select	c.1065G>A	p.Thr355Thr	synonymous	Exon 8 of 12	ENSP00000403524.3	Q7Z569-1
	BRAP	ENST00000327551.6	TSL:1	c.975G>A	p.Thr325Thr	synonymous	Exon 8 of 12	ENSP00000330813.5	J3KNN7
	BRAP	ENST00000871570.1		c.1026G>A	p.Thr342Thr	synonymous	Exon 7 of 11	ENSP00000541629.1

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

GnomAD2 exomes AF: 0.00242 AC: 607 AN: 251338 AF XY: 0.00237

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 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

African (AFR) AF: 0.000329 AC: 11 AN: 33478

American (AMR) AF: 0.00143 AC: 64 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000689 AC: 18 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39696

South Asian (SAS) AF: 0.00105 AC: 91 AN: 86258

European-Finnish (FIN) AF: 0.00500 AC: 267 AN: 53398

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5766

European-Non Finnish (NFE) AF: 0.00341 AC: 3790 AN: 1111978

Other (OTH) AF: 0.00343 AC: 207 AN: 60396

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

African (AFR) AF: 0.000505 AC: 21 AN: 41580

American (AMR) AF: 0.000917 AC: 14 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5180

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00575 AC: 61 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00369 AC: 251 AN: 68030

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.40
DANN	Benign	0.77
PhyloP100		-5.2
Mutation Taster		=99/1	polymorphism

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: rs151101195; hg19: chr12-112097057;