NM_153252.5:c.*5481A>C

Variant names:

• chrX-80671128-T-G
• rs12690214
• NM_153252.5:c.*5481A>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_153252.5(BRWD3):​c.*5481A>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 0.269 in 110,628 control chromosomes in the GnomAD database, including 2,915 homozygotes. There are 8,851 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (2915 hom., 8851 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: BRWD3 NM_153252.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.356

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=-0.97).
• BP6: Variant X-80671128-T-G is Benign according to our data. Variant chrX-80671128-T-G is described in ClinVar as [Benign]. Clinvar id is 368690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRWD3	NM_153252.5	c.*5481A>C		3_prime_UTR_variant	Exon 41 of 41	ENST00000373275.5	NP_694984.5
BRWD3	XM_005262113.4	c.*5481A>C		3_prime_UTR_variant	Exon 40 of 40		XP_005262170.1
BRWD3	XM_017029384.2	c.*5481A>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.*5481A>C		3_prime_UTR_variant	Exon 41 of 41	1	NM_153252.5	ENSP00000362372.4

Frequencies

GnomAD3 genomes AF: 0.269 AC: 29733 AN: 110575 Hom.: 2919 Cov.: 22 AF XY: 0.269 AC XY: 8839 AN XY: 32821

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.259

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.269 AC: 29737 AN: 110628 Hom.: 2915 Cov.: 22 AF XY: 0.269 AC XY: 8851 AN XY: 32884

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.621

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.257

Alfa AF: 0.254 Hom.: 1540

Bravo AF: 0.259

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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	-0.97
CADD	Benign	0.67
DANN	Benign	0.63

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: rs12690214; hg19: chrX-79926627;