X-80670583-T-TA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_153252.5(BRWD3):c.*6025_*6026insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0173 in 107,242 control chromosomes in the GnomAD database, including 21 homozygotes. There are 445 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.017 (21 hom., 445 hem., cov: 21)
• Consequence: BRWD3 NM_153252.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.846

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 -10 ACMG points.

• BP6: Variant X-80670583-T-TA is Benign according to our data. Variant chrX-80670583-T-TA is described in ClinVar as [Likely_benign]. Clinvar id is 368686.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0173 (1851/107242) while in subpopulation NFE AF= 0.0276 (1426/51688). AF 95% confidence interval is 0.0264. There are 21 homozygotes in gnomad4. There are 445 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 21 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRWD3	NM_153252.5	c.*6025_*6026insT		3_prime_UTR_variant	41/41	ENST00000373275.5
BRWD3	XM_005262113.4	c.*6025_*6026insT		3_prime_UTR_variant	40/40
BRWD3	XM_017029384.2	c.*6025_*6026insT		3_prime_UTR_variant	30/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRWD3	ENST00000373275.5	c.*6025_*6026insT		3_prime_UTR_variant	41/41	1	NM_153252.5	P1

Frequencies

GnomAD3 genomes AF: 0.0173 AC: 1851 AN: 107214 Hom.: 21 Cov.: 21 AF XY: 0.0146 AC XY: 445 AN XY: 30376

Gnomad AFR AF: 0.00421

Gnomad AMI AF: 0.0872

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.00701

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00403

Gnomad FIN AF: 0.0162

Gnomad MID AF: 0.00435

Gnomad NFE AF: 0.0276

Gnomad OTH AF: 0.0160

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

GnomAD4 genome AF: 0.0173 AC: 1851 AN: 107242 Hom.: 21 Cov.: 21 AF XY: 0.0146 AC XY: 445 AN XY: 30418

Gnomad4 AFR AF: 0.00420

Gnomad4 AMR AF: 0.0105

Gnomad4 ASJ AF: 0.00701

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00405

Gnomad4 FIN AF: 0.0162

Gnomad4 NFE AF: 0.0276

Gnomad4 OTH AF: 0.0158

Bravo AF: 0.0156

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Non-syndromic X-linked intellectual disability Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs201004001; hg19: chrX-79926082;