X-80670583-TA-TAA

Variant names:

• chrX-80670583-T-TA
• rs201004001
• NM_153252.5:c.*6025dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_153252.5(BRWD3):​c.*6025dupT 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
• Publications: 0 publications found

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]

BRWD3 Gene-Disease associations (from GenCC):

• intellectual disability, X-linked 93

  Inheritance: XL, AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• X-linked syndromic intellectual disability

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• infantile spasms

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• self-limited epilepsy with centrotemporal spikes

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 21. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1851 XL,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153252.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRWD3	NM_153252.5	MANE Select	c.*6025dupT		3_prime_UTR	Exon 41 of 41	NP_694984.5
	BRWD3	NM_001441339.1		c.*6025dupT		3_prime_UTR	Exon 40 of 40	NP_001428268.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRWD3	ENST00000373275.5	TSL:1 MANE Select	c.*6025dupT		3_prime_UTR	Exon 41 of 41	ENSP00000362372.4	Q6RI45-1

Frequencies

GnomAD3 genomes AF: 0.0173 AC: 1851 AN: 107214 Hom.: 21 Cov.: 21

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

African (AFR) AF: 0.00420 AC: 124 AN: 29497

American (AMR) AF: 0.0105 AC: 105 AN: 9982

Ashkenazi Jewish (ASJ) AF: 0.00701 AC: 18 AN: 2566

East Asian (EAS) AF: 0.00 AC: 0 AN: 3370

South Asian (SAS) AF: 0.00405 AC: 10 AN: 2467

European-Finnish (FIN) AF: 0.0162 AC: 87 AN: 5354

Middle Eastern (MID) AF: 0.00478 AC: 1 AN: 209

European-Non Finnish (NFE) AF: 0.0276 AC: 1426 AN: 51688

Other (OTH) AF: 0.0158 AC: 23 AN: 1455

Alfa AF: 0.00755 Hom.: 39

Bravo AF: 0.0156

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Non-syndromic X-linked intellectual disability (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.85

Splicing

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

Other links and lift over

dbSNP: rs201004001; hg19: chrX-79926082;