Variant 12-111679205-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006768.5(BRAP):c.579T>C(p.Ile193Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00292 in 1,608,824 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 70 hom., cov: 30)

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: 2.01

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 12-111679205-A-G is Benign according to our data. Variant chr12-111679205-A-G is described in ClinVar as [Benign]. Clinvar id is 768586.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0517 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.579T>C	p.Ile193Ile	synonymous_variant	4/12	ENST00000419234.9	NP_006759.3	Q7Z569-1Q59H81
BRAP	XM_005253944.5 linkuse as main transcript	c.702T>C	p.Ile234Ile	synonymous_variant	4/12		XP_005254001.1
BRAP	XM_017019992.2 linkuse as main transcript	c.417T>C	p.Ile139Ile	synonymous_variant	3/11		XP_016875481.1
BRAP	XM_047429622.1 linkuse as main transcript	c.132T>C	p.Ile44Ile	synonymous_variant	2/10		XP_047285578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRAP	ENST00000419234.9 linkuse as main transcript	c.579T>C	p.Ile193Ile	synonymous_variant	4/12	1	NM_006768.5	ENSP00000403524.3		Q7Z569-1
BRAP	ENST00000327551.6 linkuse as main transcript	c.489T>C	p.Ile163Ile	synonymous_variant	4/12	1		ENSP00000330813.5		J3KNN7

Frequencies

GnomAD3 genomes

AF:

0.0154

AC:

2342

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0533

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:

0.00861

GnomAD3 exomes

AF:

0.00408

AC:

1017

AN:

249532

Hom.:

AF XY:

0.00311

AC XY:

420

AN XY:

134910

show subpopulations

Gnomad AFR exome

AF:

0.0545

Gnomad AMR exome

AF:

0.00287

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000166

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.00165

GnomAD4 exome

AF:

0.00160

AC:

2333

AN:

1456590

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

979

AN XY:

724186

show subpopulations

Gnomad4 AFR exome

AF:

0.0535

Gnomad4 AMR exome

AF:

0.00295

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000141

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000110

Gnomad4 OTH exome

AF:

0.00427

GnomAD4 genome

AF:

0.0155

AC:

2361

AN:

152234

Hom.:

Cov.:

AF XY:

0.0153

AC XY:

1139

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0536

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:

0.00947

Alfa

AF:

0.00850

Hom.:

Bravo

AF:

0.0169

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

-0.54

CADD

Benign

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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