rs41271277

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001114086.2(CLIC5):c.237A>T(p.Arg79Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00359 in 1,551,702 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 16 hom. )

Consequence

CLIC5
NM_001114086.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.307

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 was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0061671734).

BP6

Variant 6-46080006-T-A is Benign according to our data. Variant chr6-46080006-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 508150.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-46080006-T-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
CLIC5	NM_001114086.2 link	c.237A>T	p.Arg79Ser	missense_variant	Exon 1 of 6	NP_001107558.1	Q9NZA1-1Q53G01
CLIC5	NM_001370650.1 link	c.237A>T	p.Arg79Ser	missense_variant	Exon 2 of 7	NP_001357579.1
CLIC5	XM_011514692.4 link	c.237A>T	p.Arg79Ser	missense_variant	Exon 1 of 7	XP_011512994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLIC5	ENST00000185206.12 link	c.237A>T	p.Arg79Ser	missense_variant	Exon 1 of 6	1		ENSP00000185206.6		Q9NZA1-1

Frequencies

GnomAD3 genomes

AF:

0.00303

AC:

461

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00452

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00497

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00273

AC:

427

AN:

156382

AF XY:

0.00276

show subpopulations

Gnomad AFR exome

AF:

0.000757

Gnomad AMR exome

AF:

0.00215

Gnomad ASJ exome

AF:

0.00153

Gnomad EAS exome

AF:

0.0000917

Gnomad FIN exome

AF:

0.000475

Gnomad NFE exome

AF:

0.00498

Gnomad OTH exome

AF:

0.00365

GnomAD4 exome

AF:

0.00366

AC:

5115

AN:

1399394

Hom.:

Cov.:

AF XY:

0.00364

AC XY:

2512

AN XY:

690206

show subpopulations

Gnomad4 AFR exome

AF:

0.000570

AC:

AN:

31598

Gnomad4 AMR exome

AF:

0.00238

AC:

AN:

35702

Gnomad4 ASJ exome

AF:

0.00159

AC:

AN:

25182

Gnomad4 EAS exome

AF:

0.0000280

AC:

AN:

35738

Gnomad4 SAS exome

AF:

0.00105

AC:

AN:

79236

Gnomad4 FIN exome

AF:

0.000406

AC:

AN:

49274

Gnomad4 NFE exome

AF:

0.00433

AC:

4668

AN:

1078964

Gnomad4 Remaining exome

AF:

0.00309

AC:

179

AN:

58002

Heterozygous variant carriers

319

639

958

1278

1597

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

162

324

486

648

810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00303

AC:

461

AN:

152308

Hom.:

Cov.:

AF XY:

0.00279

AC XY:

208

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000746

AC:

0.000745551

AN:

0.000745551

Gnomad4 AMR

AF:

0.00451

AC:

0.00451275

AN:

0.00451275

Gnomad4 ASJ

AF:

0.00202

AC:

0.00201729

AN:

0.00201729

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.000622

AC:

0.000622407

AN:

0.000622407

Gnomad4 FIN

AF:

0.000282

AC:

0.000282486

AN:

0.000282486

Gnomad4 NFE

AF:

0.00495

AC:

0.00495413

AN:

0.00495413

Gnomad4 OTH

AF:

0.00473

AC:

0.00473037

AN:

0.00473037

Heterozygous variant carriers

107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00395

Hom.:

Bravo

AF:

0.00309

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.00471

AC:

ExAC

AF:

0.00266

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 20, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CLIC5: BP4, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Aug 23, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Arg79Ser in exon 1 of CLIC5: This variant is not expected to have clinical sig nificance because it has been identified in 0.52% (46/8766) of European chromoso mes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; d bSNP rs41271277). -

Autosomal recessive nonsyndromic hearing loss 103

Benign:1

Aug 07, 2018

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.4

DANN

Benign

0.82

DEOGEN2

Benign

0.021

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.38

M_CAP

Benign

0.0051

MetaRNN

Benign

0.0062

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.22

PROVEAN

Benign

0.41

REVEL

Benign

0.012

Sift

Benign

0.41

Sift4G

Benign

0.54

Polyphen

0.0010

Vest4

0.077

MutPred

0.29

Gain of glycosylation at R79 (P = 0.0048);

MVP

0.16

MPC

0.13

ClinPred

0.00060

GERP RS

2.4

Varity_R

0.075

gMVP

0.091

Mutation Taster

=100/0

polymorphism

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