X-80744022-C-G

Position:

chrX-80744022-C-G

Variant summary

Our verdict is Benign. Variant got -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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 21 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
BRWD3	NM_153252.5 linkuse as main transcript	c.813+10G>C	intron_variant	ENST00000373275.5	NP_694984.5
BRWD3	XM_005262113.4 linkuse as main transcript	c.813+10G>C	intron_variant		XP_005262170.1
BRWD3	XM_017029385.3 linkuse as main transcript	c.813+10G>C	intron_variant		XP_016884874.1
BRWD3	XM_047441957.1 linkuse as main transcript	c.813+10G>C	intron_variant		XP_047297913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRWD3	ENST00000373275.5 linkuse as main transcript	c.813+10G>C		intron_variant		1	NM_153252.5	ENSP00000362372	P1	Q6RI45-1
BRWD3	ENST00000478415.1 linkuse as main transcript	n.1035G>C		non_coding_transcript_exon_variant	8/8	5

Frequencies

GnomAD3 genomes

AF:

0.0184

AC:

2048

AN:

111558

Hom.:

Cov.:

AF XY:

0.0162

AC XY:

548

AN XY:

33742

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

GnomAD3 exomes

AF:

0.0194

AC:

3487

AN:

180103

Hom.:

AF XY:

0.0197

AC XY:

1281

AN XY:

64939

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 SAS exome

AF:

0.00327

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

Gnomad4 AFR exome

AF:

0.00372

Gnomad4 AMR exome

AF:

0.0169

Gnomad4 ASJ exome

AF:

0.0498

Gnomad4 EAS exome

AF:

0.0000664

Gnomad4 SAS exome

AF:

0.00394

Gnomad4 FIN exome

AF:

0.0286

Gnomad4 NFE exome

AF:

0.0250

Gnomad4 OTH exome

AF:

0.0245

GnomAD4 genome

AF:

0.0183

AC:

2048

AN:

111610

Hom.:

Cov.:

AF XY:

0.0162

AC XY:

548

AN XY:

33804

show subpopulations

Gnomad4 AFR

AF:

0.00345

Gnomad4 AMR

AF:

0.0230

Gnomad4 ASJ

AF:

0.0458

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00334

Gnomad4 FIN

AF:

0.0265

Gnomad4 NFE

AF:

0.0253

Gnomad4 OTH

AF:

0.0271

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

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 15, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Dec 11, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 26, 2012	- -

BRWD3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 11, 2019

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

DANN

Benign

0.75

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