Variant 6-45912742-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001256023.2(CLIC5):c.589-3T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00315 in 1,529,020 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0063 ( 29 hom., cov: 33)

Exomes 𝑓: 0.0028 ( 106 hom. )

Consequence

CLIC5
NM_001256023.2 splice_region, intron

Scores

Splicing: ADA: 0.00002056

Clinical Significance

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

Conservation

PhyloP100: 0.0950

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 6-45912742-A-G is Benign according to our data. Variant chr6-45912742-A-G is described in ClinVar as [Benign]. Clinvar id is 666619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIC5	NM_016929.5 link	c.588+1486T>C		intron_variant	Intron 5 of 5	ENST00000339561.12	NP_058625.2	Q9NZA1-2Q53G01

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLIC5	ENST00000339561.12 link	c.588+1486T>C		intron_variant	Intron 5 of 5	1	NM_016929.5	ENSP00000344165.6		Q9NZA1-2

Frequencies

GnomAD3 genomes

AF:

0.00626

AC:

953

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0457

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0222

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00847

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.0136

AC:

1877

AN:

137788

Hom.:

AF XY:

0.0109

AC XY:

817

AN XY:

74616

show subpopulations

Gnomad AFR exome

AF:

0.000751

Gnomad AMR exome

AF:

0.0633

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0212

Gnomad SAS exome

AF:

0.00129

Gnomad FIN exome

AF:

0.00571

Gnomad NFE exome

AF:

0.0000738

Gnomad OTH exome

AF:

0.00710

GnomAD4 exome

AF:

0.00280

AC:

3854

AN:

1376698

Hom.:

106

Cov.:

AF XY:

0.00257

AC XY:

1744

AN XY:

679876

show subpopulations

Gnomad4 AFR exome

AF:

0.000350

Gnomad4 AMR exome

AF:

0.0577

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0346

Gnomad4 SAS exome

AF:

0.00116

Gnomad4 FIN exome

AF:

0.00581

Gnomad4 NFE exome

AF:

0.0000848

Gnomad4 OTH exome

AF:

0.00300

GnomAD4 genome

AF:

0.00628

AC:

957

AN:

152322

Hom.:

Cov.:

AF XY:

0.00787

AC XY:

586

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.0458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0226

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.00847

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00190

Hom.:

Bravo

AF:

0.00807

Asia WGS

AF:

0.00866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 23, 2017

c.589-3T>C in intron 5 of CLIC5: This variant is not expected to have clinical s ignificance because it has been identified in 2.78% (5/180) of Latino chromosome s by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbS NP rs75780343). -

CLIC5-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 24, 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). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.0

DANN

Benign

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000021

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.020

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