Variant chr12-111650001-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_006768.5(BRAP):c.1353G>A(p.Lys451Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00288 in 1,611,846 control chromosomes in the GnomAD database, including 123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 72 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 51 hom. )

Consequence

BRAP
NM_006768.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.124

Variant links:

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]

BRAP links:

BRAP (HGNC:):

BRAP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 12-111650001-C-T is Benign according to our data. Variant chr12-111650001-C-T is described in ClinVar as [Benign]. Clinvar id is 768584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.124 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRAP	NM_006768.5 linkuse as main transcript	c.1353G>A	p.Lys451Lys	synonymous_variant	11/12	ENST00000419234.9	NP_006759.3	Q7Z569-1Q59H81

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BRAP	ENST00000419234.9 linkuse as main transcript	c.1353G>A	p.Lys451Lys	synonymous_variant	11/12	1	NM_006768.5	ENSP00000403524.3	Q7Z569-1
BRAP	ENST00000327551.6 linkuse as main transcript	c.1263G>A	p.Lys421Lys	synonymous_variant	11/12	1		ENSP00000330813.5	J3KNN7
BRAP	ENST00000547043.1 linkuse as main transcript	n.1257G>A		non_coding_transcript_exon_variant	7/8	3

Frequencies

GnomAD3 genomes

AF:

0.0153

AC:

2335

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00642

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00402

AC:

1008

AN:

250524

Hom.:

AF XY:

0.00305

AC XY:

413

AN XY:

135380

show subpopulations

Gnomad AFR exome

AF:

0.0541

Gnomad AMR exome

AF:

0.00279

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000165

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00157

AC:

2296

AN:

1459546

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

962

AN XY:

726122

show subpopulations

Gnomad4 AFR exome

AF:

0.0527

Gnomad4 AMR exome

AF:

0.00289

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000140

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000109

Gnomad4 OTH exome

AF:

0.00419

GnomAD4 genome

AF:

0.0154

AC:

2353

AN:

152300

Hom.:

Cov.:

AF XY:

0.0152

AC XY:

1133

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0533

Gnomad4 AMR

AF:

0.00641

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00946

Alfa

AF:

0.00674

Hom.:

Bravo

AF:

0.0168

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 08, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

4.7

DANN

Benign

0.59

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over