Variant 6-46079721-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000185206.12(CLIC5):c.522G>A(p.Glu174=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,550,866 control chromosomes in the GnomAD database, including 25,083 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1970 hom., cov: 33)

Exomes 𝑓: 0.17 ( 23113 hom. )

Consequence

CLIC5
ENST00000185206.12 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.04

Variant links:

Genes affected

CLIC5 (HGNC:13517): (chloride intracellular channel 5) This gene encodes a member of the chloride intracellular channel (CLIC) family of chloride ion channels. The encoded protein associates with actin-based cytoskeletal structures and may play a role in multiple processes including hair cell stereocilia formation, myoblast proliferation and glomerular podocyte and endothelial cell maintenance. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

CLIC5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 6-46079721-C-T is Benign according to our data. Variant chr6-46079721-C-T is described in ClinVar as [Benign]. Clinvar id is 508561.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.04 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons
CLIC5	NM_001114086.2 linkuse as main transcript	c.522G>A	p.Glu174=	synonymous_variant	1/6
CLIC5	NM_001370650.1 linkuse as main transcript	c.522G>A	p.Glu174=	synonymous_variant	2/7
CLIC5	XM_011514692.4 linkuse as main transcript	c.522G>A	p.Glu174=	synonymous_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLIC5	ENST00000185206.12 linkuse as main transcript	c.522G>A	p.Glu174=	synonymous_variant	1/6	1			Q9NZA1-1

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

21324

AN:

152098

Hom.:

1968

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0517

Gnomad AMI

AF:

0.181

Gnomad AMR

AF:

0.127

Gnomad ASJ

AF:

0.235

Gnomad EAS

AF:

0.330

Gnomad SAS

AF:

0.333

Gnomad FIN

AF:

0.155

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.141

GnomAD3 exomes

AF:

0.186

AC:

28979

AN:

155996

Hom.:

3329

AF XY:

0.198

AC XY:

16355

AN XY:

82520

show subpopulations

Gnomad AFR exome

AF:

0.0466

Gnomad AMR exome

AF:

0.102

Gnomad ASJ exome

AF:

0.242

Gnomad EAS exome

AF:

0.317

Gnomad SAS exome

AF:

0.334

Gnomad FIN exome

AF:

0.147

Gnomad NFE exome

AF:

0.162

Gnomad OTH exome

AF:

0.178

GnomAD4 exome

AF:

0.172

AC:

240325

AN:

1398650

Hom.:

23113

Cov.:

AF XY:

0.177

AC XY:

122074

AN XY:

689800

show subpopulations

Gnomad4 AFR exome

AF:

0.0431

Gnomad4 AMR exome

AF:

0.105

Gnomad4 ASJ exome

AF:

0.243

Gnomad4 EAS exome

AF:

0.338

Gnomad4 SAS exome

AF:

0.332

Gnomad4 FIN exome

AF:

0.151

Gnomad4 NFE exome

AF:

0.159

Gnomad4 OTH exome

AF:

0.176

GnomAD4 genome

AF:

0.140

AC:

21331

AN:

152216

Hom.:

1970

Cov.:

AF XY:

0.143

AC XY:

10676

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0518

Gnomad4 AMR

AF:

0.127

Gnomad4 ASJ

AF:

0.235

Gnomad4 EAS

AF:

0.331

Gnomad4 SAS

AF:

0.332

Gnomad4 FIN

AF:

0.155

Gnomad4 NFE

AF:

0.161

Gnomad4 OTH

AF:

0.145

Alfa

AF:

0.160

Hom.:

1682

Bravo

AF:

0.129

Asia WGS

AF:

0.336

AC:

1166

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Aug 23, 2017	p.Glu174Glu in exon 1 of CLIC5: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 34.27% (2608/7610) o f South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac .broadinstitute.org; dbSNP rs3734207). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

5.6

DANN

Benign

0.27

Splicing

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