X-80670278-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_153252.5(BRWD3):c.*6331C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 110,691 control chromosomes in the GnomAD database, including 1,149 homozygotes. There are 5,511 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (1149 hom., 5511 hem., cov: 21)
• Consequence: BRWD3 NM_153252.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.665

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant X-80670278-G-C is Benign according to our data. Variant chrX-80670278-G-C is described in ClinVar as [Benign]. Clinvar id is 914166.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRWD3	NM_153252.5	c.*6331C>G		3_prime_UTR_variant	41/41	ENST00000373275.5
BRWD3	XM_005262113.4	c.*6331C>G		3_prime_UTR_variant	40/40
BRWD3	XM_017029384.2	c.*6331C>G		3_prime_UTR_variant	30/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRWD3	ENST00000373275.5	c.*6331C>G		3_prime_UTR_variant	41/41	1	NM_153252.5	P1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 18206 AN: 110638 Hom.: 1151 Cov.: 21 AF XY: 0.167 AC XY: 5501 AN XY: 32910

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.0907

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.147

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.165 AC: 18217 AN: 110691 Hom.: 1149 Cov.: 21 AF XY: 0.167 AC XY: 5511 AN XY: 32973

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.0906

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.147

Alfa AF: 0.0612 Hom.: 309

Bravo AF: 0.158

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual disability, X-linked 93 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.020
Dann	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11266586; hg19: chrX-79925777;