rs55824836

Variant names:

• chrX-80744022-C-G
• rs55824836
• NM_153252.5:c.813+10G>C

Your query was ambiguous. Multiple possible variants found:

• chrX-80744022-C-G
• chrX-80744022-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.0210

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]

ACMG classification

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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRWD3	NM_153252.5	c.813+10G>C		intron_variant	Intron 8 of 40	ENST00000373275.5	NP_694984.5
BRWD3	XM_005262113.4	c.813+10G>C		intron_variant	Intron 8 of 39		XP_005262170.1
BRWD3	XM_047441957.1	c.813+10G>C		intron_variant	Intron 8 of 37		XP_047297913.1
BRWD3	XM_017029385.3	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	c.813+10G>C		intron_variant	Intron 8 of 40	1	NM_153252.5	ENSP00000362372.4
BRWD3	ENST00000478415.1	n.1035G>C		non_coding_transcript_exon_variant	Exon 8 of 8	5

Frequencies

GnomAD3 genomes AF: 0.0184 AC: 2048 AN: 111558 Hom.: 21 Cov.: 23 AF XY: 0.0162 AC XY: 548 AN XY: 33742

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.: 33 AF XY: 0.0197 AC XY: 1281 AN XY: 64939

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.: 27 AF XY: 0.0229 AC XY: 8013 AN XY: 349619

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.: 21 Cov.: 23 AF XY: 0.0162 AC XY: 548 AN XY: 33804

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

Submissions by phenotype

not provided Benign:3

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

- -

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
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

Other links and lift over

dbSNP: rs55824836; hg19: chrX-79999521;