X-80670616-C-G

Variant names:

• chrX-80670616-C-G
• rs7065450
• NM_153252.5:c.*5993G>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.*5993G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 109,484 control chromosomes in the GnomAD database, including 1,155 homozygotes. There are 5,175 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 (1155 hom., 5175 hem., cov: 21)
• Consequence: BRWD3 NM_153252.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0560

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=-0.94).
• BP6: Variant X-80670616-C-G is Benign according to our data. Variant chrX-80670616-C-G is described in ClinVar as [Benign]. Clinvar id is 368687.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRWD3	NM_153252.5	c.*5993G>C		3_prime_UTR_variant	Exon 41 of 41	ENST00000373275.5	NP_694984.5
BRWD3	XM_005262113.4	c.*5993G>C		3_prime_UTR_variant	Exon 40 of 40		XP_005262170.1
BRWD3	XM_017029384.2	c.*5993G>C		3_prime_UTR_variant	Exon 30 of 30		XP_016884873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRWD3	ENST00000373275	c.*5993G>C		3_prime_UTR_variant	Exon 41 of 41	1	NM_153252.5	ENSP00000362372.4

Frequencies

GnomAD3 genomes AF: 0.163 AC: 17858 AN: 109431 Hom.: 1157 Cov.: 21 AF XY: 0.163 AC XY: 5164 AN XY: 31761

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.0907

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.163 AC: 17870 AN: 109484 Hom.: 1155 Cov.: 21 AF XY: 0.163 AC XY: 5175 AN XY: 31824

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.0906

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.143

Alfa AF: 0.143 Hom.: 803

Bravo AF: 0.157

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual disability, X-linked 93 Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.94
CADD	Benign	1.2
DANN	Benign	0.28

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7065450; hg19: chrX-79926115;