rs187384754

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_153252.5(BRWD3):c.573C>T(p.Ser191Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000986 in 1,206,455 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 42 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., 5 hem., cov: 23)

Exomes 𝑓: 0.000093 ( 0 hom. 37 hem. )

Consequence

BRWD3
NM_153252.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.448

Publications

0 publications found

Variant links:

Genes affected

BRWD3 (HGNC:17342): (bromodomain and WD repeat domain containing 3) The protein encoded by this gene contains a bromodomain and several WD repeats. It is thought to have a chromatin-modifying function, and may thus play a role in transcription. Mutations in this gene are associated with a spectrum of cognitive disabilities and X-linked macrocephaly. This gene is also associated with translocations in patients with B-cell chronic lymphocytic leukemia. [provided by RefSeq, Jul 2017]

BRWD3 Gene-Disease associations (from GenCC):

intellectual disability, X-linked 93
Inheritance: XL, AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
X-linked syndromic intellectual disability
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
infantile spasms
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
self-limited epilepsy with centrotemporal spikes
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

BRWD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant X-80745587-G-A is Benign according to our data. Variant chrX-80745587-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 434542.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.448 with no splicing effect.

BS2

High AC in GnomAd4 at 17 XL,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRWD3	NM_153252.5 link	c.573C>T	p.Ser191Ser	synonymous_variant	Exon 7 of 41	ENST00000373275.5	NP_694984.5	Q6RI45-1
BRWD3	NM_001441339.1 link	c.573C>T	p.Ser191Ser	synonymous_variant	Exon 7 of 40		NP_001428268.1
BRWD3	XM_047441957.1 link	c.573C>T	p.Ser191Ser	synonymous_variant	Exon 7 of 38		XP_047297913.1
BRWD3	XM_017029385.3 link	c.573C>T	p.Ser191Ser	synonymous_variant	Exon 7 of 22		XP_016884874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRWD3	ENST00000373275.5 link	c.573C>T	p.Ser191Ser	synonymous_variant	Exon 7 of 41	1	NM_153252.5	ENSP00000362372.4		Q6RI45-1
BRWD3	ENST00000478415.1 link	n.785C>T		non_coding_transcript_exon_variant	Exon 7 of 8	5

Frequencies

GnomAD3 genomes

AF:

0.000163

AC:

AN:

110522

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000973

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000173

Gnomad MID

AF:

0.00844

Gnomad NFE

AF:

0.000208

Gnomad OTH

AF:

0.00201

GnomAD2 exomes

AF:

0.000173

AC:

AN:

179689

AF XY:

0.000201

show subpopulations

Gnomad AFR exome

AF:

0.0000772

Gnomad AMR exome

AF:

0.0000738

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000313

Gnomad OTH exome

AF:

0.000226

GnomAD4 exome

AF:

0.0000931

AC:

102

AN:

1095881

Hom.:

Cov.:

AF XY:

0.000102

AC XY:

AN XY:

361651

show subpopulations

African (AFR)

AF:

0.0000759

AC:

AN:

26340

American (AMR)

AF:

0.0000856

AC:

AN:

35055

Ashkenazi Jewish (ASJ)

AF:

0.0000517

AC:

AN:

19329

East Asian (EAS)

AF:

0.0000332

AC:

AN:

30101

South Asian (SAS)

AF:

0.0000186

AC:

AN:

53849

European-Finnish (FIN)

AF:

0.0000247

AC:

AN:

40441

Middle Eastern (MID)

AF:

0.000242

AC:

AN:

4127

European-Non Finnish (NFE)

AF:

0.000101

AC:

AN:

840648

Other (OTH)

AF:

0.000152

AC:

AN:

45991

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000154

AC:

AN:

110574

Hom.:

Cov.:

AF XY:

0.000152

AC XY:

AN XY:

32908

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30416

American (AMR)

AF:

0.0000972

AC:

AN:

10287

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2636

East Asian (EAS)

AF:

0.00

AC:

AN:

3510

South Asian (SAS)

AF:

0.00

AC:

AN:

2601

European-Finnish (FIN)

AF:

0.000173

AC:

AN:

5796

Middle Eastern (MID)

AF:

0.00461

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.000208

AC:

AN:

52918

Other (OTH)

AF:

0.00198

AC:

AN:

1513

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000260

Hom.:

Bravo

AF:

0.000162

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

BRWD3: BP4, BP7 -

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 03, 2017

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

BRWD3-related disorder

Benign:1

Jun 13, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

-0.45

CADD

Benign

5.2

(source)

DANN

Benign

0.67

PhyloP100

0.45

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs187384754

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over