Variant chr3-184346596-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_004366.6(CLCN2):c.*10G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 1,613,700 control chromosomes in the GnomAD database, including 152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0087 ( 14 hom., cov: 32)

Exomes 𝑓: 0.012 ( 138 hom. )

Consequence

CLCN2
NM_004366.6 3_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.28

Variant links:

Genes affected

CLCN2 (HGNC:2020): (chloride voltage-gated channel 2) This gene encodes a voltage-gated chloride channel. The encoded protein is a transmembrane protein that maintains chloride ion homeostasis in various cells. Defects in this gene may be a cause of certain epilepsies. Four transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2012]

CLCN2 links:

FAM131A (HGNC:28308): (family with sequence similarity 131 member A)

FAM131A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 3-184346596-C-T is Benign according to our data. Variant chr3-184346596-C-T is described in ClinVar as [Benign]. Clinvar id is 3038389.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00867 (1320/152290) while in subpopulation NFE AF= 0.0137 (934/68010). AF 95% confidence interval is 0.013. There are 14 homozygotes in gnomad4. There are 642 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1320 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCN2	NM_004366.6 linkuse as main transcript	c.*10G>A		3_prime_UTR_variant	24/24	ENST00000265593.9	NP_004357.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCN2	ENST00000265593.9 linkuse as main transcript	c.*10G>A		3_prime_UTR_variant	24/24	1	NM_004366.6	ENSP00000265593	P1	P51788-1

Frequencies

GnomAD3 genomes

AF:

0.00869

AC:

1322

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00277

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.00596

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.00593

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0137

Gnomad OTH

AF:

0.00908

GnomAD3 exomes

AF:

0.00889

AC:

2226

AN:

250404

Hom.:

AF XY:

0.00900

AC XY:

1219

AN XY:

135464

show subpopulations

Gnomad AFR exome

AF:

0.00321

Gnomad AMR exome

AF:

0.00500

Gnomad ASJ exome

AF:

0.0157

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00359

Gnomad FIN exome

AF:

0.00528

Gnomad NFE exome

AF:

0.0138

Gnomad OTH exome

AF:

0.00995

GnomAD4 exome

AF:

0.0120

AC:

17559

AN:

1461410

Hom.:

138

Cov.:

AF XY:

0.0119

AC XY:

8616

AN XY:

727032

show subpopulations

Gnomad4 AFR exome

AF:

0.00254

Gnomad4 AMR exome

AF:

0.00564

Gnomad4 ASJ exome

AF:

0.0156

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00446

Gnomad4 FIN exome

AF:

0.00594

Gnomad4 NFE exome

AF:

0.0138

Gnomad4 OTH exome

AF:

0.0115

GnomAD4 genome

AF:

0.00867

AC:

1320

AN:

152290

Hom.:

Cov.:

AF XY:

0.00862

AC XY:

642

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00277

Gnomad4 AMR

AF:

0.00595

Gnomad4 ASJ

AF:

0.0150

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00352

Gnomad4 FIN

AF:

0.00593

Gnomad4 NFE

AF:

0.0137

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.0111

Hom.:

Bravo

AF:

0.00881

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CLCN2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 05, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

8.0

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over