X-80670452-G-A

Position:

• chrX-80670452-G-A

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.*6157C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0217 in 110,265 control chromosomes in the GnomAD database, including 116 homozygotes. There are 692 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.022 (116 hom., 692 hem., cov: 21)
• Consequence: BRWD3 NM_153252.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.400

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=-0.81).
• BP6: Variant X-80670452-G-A is Benign according to our data. Variant chrX-80670452-G-A is described in ClinVar as [Benign]. Clinvar id is 368685.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRWD3	NM_153252.5	c.*6157C>T		3_prime_UTR_variant	41/41	ENST00000373275.5	NP_694984.5
BRWD3	XM_005262113.4	c.*6157C>T		3_prime_UTR_variant	40/40		XP_005262170.1
BRWD3	XM_017029384.2	c.*6157C>T		3_prime_UTR_variant	30/30		XP_016884873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRWD3	ENST00000373275.5	c.*6157C>T		3_prime_UTR_variant	41/41	1	NM_153252.5	ENSP00000362372	P1

Frequencies

GnomAD3 genomes AF: 0.0216 AC: 2382 AN: 110210 Hom.: 116 Cov.: 21 AF XY: 0.0211 AC XY: 686 AN XY: 32468

Gnomad AFR AF: 0.00459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0160

Gnomad EAS AF: 0.00171

Gnomad SAS AF: 0.00234

Gnomad FIN AF: 0.0148

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0112

Gnomad OTH AF: 0.0339

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

GnomAD4 genome AF: 0.0217 AC: 2389 AN: 110265 Hom.: 116 Cov.: 21 AF XY: 0.0213 AC XY: 692 AN XY: 32533

Gnomad4 AFR AF: 0.00458

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.0160

Gnomad4 EAS AF: 0.00172

Gnomad4 SAS AF: 0.00235

Gnomad4 FIN AF: 0.0148

Gnomad4 NFE AF: 0.0112

Gnomad4 OTH AF: 0.0334

Alfa AF: 0.0250 Hom.: 130

Bravo AF: 0.0341

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	-0.81
CADD	Benign	3.7
DANN	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs142555243; hg19: chrX-79925951;