Variant chr21-39196550-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_033656.4(BRWD1):c.6519T>C(p.Asn2173=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0043 in 1,613,584 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0030 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0044 ( 18 hom. )

Consequence

BRWD1
NM_033656.4 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.129

Variant links:

Genes affected

BRWD1 (HGNC:12760): (bromodomain and WD repeat domain containing 1) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD) residues which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes including cell cycle progression, signal transduction, apoptosis, and gene regulation. This protein contains 2 bromodomains and multiple WD repeats. This gene is located within the Down syndrome region-2 on chromosome 21. Alternative splicing of this gene generates multiple transcript variants encoding distinct isoforms. In mouse, this gene encodes a nuclear protein that has a polyglutamine-containing region that functions as a transcriptional activation domain which may regulate chromatin remodelling and associates with a component of the SWI/SNF chromatin remodelling complex.[provided by RefSeq, Jun 2011]

BRWD1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 21-39196550-A-G is Benign according to our data. Variant chr21-39196550-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3033349.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.129 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRWD1	NM_033656.4 linkuse as main transcript	c.6519T>C	p.Asn2173=	synonymous_variant	41/41	ENST00000342449.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRWD1	ENST00000342449.8 linkuse as main transcript	c.6519T>C	p.Asn2173=	synonymous_variant	41/41	1	NM_033656.4	A2	Q9NSI6-2
BRWD1	ENST00000333229.6 linkuse as main transcript	c.6519T>C	p.Asn2173=	synonymous_variant	41/42	1		P2	Q9NSI6-1
BRWD1	ENST00000380800.7 linkuse as main transcript	c.6519T>C	p.Asn2173=	synonymous_variant	41/42	1		A2	Q9NSI6-3
BRWD1	ENST00000446924.5 linkuse as main transcript	c.*2843T>C		3_prime_UTR_variant, NMD_transcript_variant	25/26	2

Frequencies

GnomAD3 genomes

AF:

0.00303

AC:

461

AN:

151982

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000701

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00276

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00406

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00502

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00305

AC:

763

AN:

250356

Hom.:

AF XY:

0.00274

AC XY:

371

AN XY:

135296

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.00261

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000393

Gnomad FIN exome

AF:

0.00496

Gnomad NFE exome

AF:

0.00464

Gnomad OTH exome

AF:

0.00230

GnomAD4 exome

AF:

0.00443

AC:

6478

AN:

1461486

Hom.:

Cov.:

AF XY:

0.00424

AC XY:

3082

AN XY:

727028

show subpopulations

Gnomad4 AFR exome

AF:

0.000867

Gnomad4 AMR exome

AF:

0.00284

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.00472

Gnomad4 NFE exome

AF:

0.00524

Gnomad4 OTH exome

AF:

0.00363

GnomAD4 genome

AF:

0.00303

AC:

461

AN:

152098

Hom.:

Cov.:

AF XY:

0.00285

AC XY:

212

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.000699

Gnomad4 AMR

AF:

0.00275

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00406

Gnomad4 NFE

AF:

0.00502

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00386

Hom.:

Bravo

AF:

0.00255

EpiCase

AF:

0.00523

EpiControl

AF:

0.00433

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

BRWD1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 28, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.3

DANN

Benign

0.62

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