X-80670616-C-G

Variant names:

• chrX-80670616-C-G
• rs7065450
• NM_153252.5:c.*5993G>C

Variant summary

Our verdict is Benign. The variant received -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
• 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 -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 VariationId 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.

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.*5993G>C		3_prime_UTR	Exon 41 of 41	NP_694984.5
	BRWD3	NM_001441339.1		c.*5993G>C		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.*5993G>C		3_prime_UTR	Exon 41 of 41	ENSP00000362372.4	Q6RI45-1

Frequencies

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

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

African (AFR) AF: 0.205 AC: 6153 AN: 30000

American (AMR) AF: 0.0906 AC: 931 AN: 10279

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 370 AN: 2621

East Asian (EAS) AF: 0.217 AC: 740 AN: 3415

South Asian (SAS) AF: 0.425 AC: 1061 AN: 2494

European-Finnish (FIN) AF: 0.177 AC: 1002 AN: 5670

Middle Eastern (MID) AF: 0.184 AC: 40 AN: 217

European-Non Finnish (NFE) AF: 0.137 AC: 7225 AN: 52626

Other (OTH) AF: 0.143 AC: 213 AN: 1493

Alfa AF: 0.143 Hom.: 803

Bravo AF: 0.157

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Intellectual disability, X-linked 93 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.28
PhyloP100		0.056

Splicing

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

Other links and lift over

dbSNP: rs7065450; hg19: chrX-79926115;