rs55824836

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_153252.5(BRWD3):c.813+10G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0226 in 1,194,197 control chromosomes in the GnomAD database, including 250 homozygotes. There are 8,561 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 0.018 ( 21 hom., 548 hem., cov: 23)

Exomes 𝑓: 0.023 ( 229 hom. 8013 hem. )

Consequence

BRWD3
NM_153252.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.0210

Publications

1 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant X-80744022-C-G is Benign according to our data. Variant chrX-80744022-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 96518.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0183 (2048/111610) while in subpopulation NFE AF = 0.0253 (1342/53080). AF 95% confidence interval is 0.0242. There are 21 homozygotes in GnomAd4. There are 548 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.

BS2

High AC in GnomAd4 at 2048 XL,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
BRWD3	NM_153252.5 link	c.813+10G>C	intron_variant	Intron 8 of 40	ENST00000373275.5	NP_694984.5	Q6RI45-1
BRWD3	NM_001441339.1 link	c.813+10G>C	intron_variant	Intron 8 of 39		NP_001428268.1
BRWD3	XM_047441957.1 link	c.813+10G>C	intron_variant	Intron 8 of 37		XP_047297913.1
BRWD3	XM_017029385.3 link	c.813+10G>C	intron_variant	Intron 8 of 21		XP_016884874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRWD3	ENST00000373275.5 link	c.813+10G>C		intron_variant	Intron 8 of 40	1	NM_153252.5	ENSP00000362372.4		Q6RI45-1
BRWD3	ENST00000478415.1 link	n.1035G>C		non_coding_transcript_exon_variant	Exon 8 of 8	5

Frequencies

GnomAD3 genomes

AF:

0.0184

AC:

2048

AN:

111558

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00345

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.0231

Gnomad ASJ

AF:

0.0458

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00333

Gnomad FIN

AF:

0.0265

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0253

Gnomad OTH

AF:

0.0275

GnomAD2 exomes

AF:

0.0194

AC:

3487

AN:

180103

AF XY:

0.0197

show subpopulations

Gnomad AFR exome

AF:

0.00275

Gnomad AMR exome

AF:

0.0155

Gnomad ASJ exome

AF:

0.0451

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0299

Gnomad NFE exome

AF:

0.0255

Gnomad OTH exome

AF:

0.0270

GnomAD4 exome

AF:

0.0230

AC:

24948

AN:

1082587

Hom.:

229

Cov.:

AF XY:

0.0229

AC XY:

8013

AN XY:

349619

show subpopulations

African (AFR)

AF:

0.00372

AC:

AN:

26060

American (AMR)

AF:

0.0169

AC:

589

AN:

34855

Ashkenazi Jewish (ASJ)

AF:

0.0498

AC:

955

AN:

19179

East Asian (EAS)

AF:

0.0000664

AC:

AN:

30123

South Asian (SAS)

AF:

0.00394

AC:

210

AN:

53239

European-Finnish (FIN)

AF:

0.0286

AC:

1160

AN:

40507

Middle Eastern (MID)

AF:

0.0211

AC:

AN:

4084

European-Non Finnish (NFE)

AF:

0.0250

AC:

20731

AN:

828942

Other (OTH)

AF:

0.0245

AC:

1118

AN:

45598

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

853

1707

2560

3414

4267

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

772

1544

2316

3088

3860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0183

AC:

2048

AN:

111610

Hom.:

Cov.:

AF XY:

0.0162

AC XY:

548

AN XY:

33804

show subpopulations

African (AFR)

AF:

0.00345

AC:

106

AN:

30759

American (AMR)

AF:

0.0230

AC:

241

AN:

10462

Ashkenazi Jewish (ASJ)

AF:

0.0458

AC:

121

AN:

2643

East Asian (EAS)

AF:

0.00

AC:

AN:

3570

South Asian (SAS)

AF:

0.00334

AC:

AN:

2697

European-Finnish (FIN)

AF:

0.0265

AC:

159

AN:

5996

Middle Eastern (MID)

AF:

0.0279

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.0253

AC:

1342

AN:

53080

Other (OTH)

AF:

0.0271

AC:

AN:

1511

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

140

211

281

351

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0244

Hom.:

194

Bravo

AF:

0.0185

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Nov 15, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Nov 26, 2012

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 11, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

BRWD3-related disorder

Benign:1

Apr 11, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Intellectual disability, X-linked 93

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

2.4

(source)

DANN

Benign

0.75

PhyloP100

-0.021

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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