X-80669747-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_153252.5(BRWD3):c.*6862T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.62 (16426 hom., 19743 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: BRWD3 NM_153252.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.46

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant X-80669747-A-G is Benign according to our data. Variant chrX-80669747-A-G is described in ClinVar as [Benign]. Clinvar id is 368680.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 16433 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRWD3	NM_153252.5	c.*6862T>C		3_prime_UTR_variant	41/41	ENST00000373275.5
BRWD3	XM_005262113.4	c.*6862T>C		3_prime_UTR_variant	40/40
BRWD3	XM_017029384.2	c.*6862T>C		3_prime_UTR_variant	30/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRWD3	ENST00000373275.5	c.*6862T>C		3_prime_UTR_variant	41/41	1	NM_153252.5	P1

Frequencies

GnomAD3 genomes AF: 0.624 AC: 68597 AN: 109898 Hom.: 16433 Cov.: 22 AF XY: 0.612 AC XY: 19721 AN XY: 32224

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.641

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.624 AC: 68610 AN: 109952 Hom.: 16426 Cov.: 22 AF XY: 0.611 AC XY: 19743 AN XY: 32288

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.711

Gnomad4 EAS AF: 0.598

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.684

Gnomad4 NFE AF: 0.748

Gnomad4 OTH AF: 0.641

Alfa AF: 0.681 Hom.: 6171

Bravo AF: 0.627

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	-0.32
Cadd	Benign	12
Dann	Benign	0.95

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2063579; hg19: chrX-79925246;