dbSNP rs3734207: CLIC5:p.Glu174Glu (chr6-46079721-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001114086.2(CLIC5):c.522G>A(p.Glu174Glu) 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
NM_001114086.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.04

Publications

14 publications found

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 Gene-Disease associations (from GenCC):

hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive nonsyndromic hearing loss 103
Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

CLIC5 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001114086.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001114086.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLIC5	NM_001114086.2	c.522G>A	p.Glu174Glu	synonymous	Exon 1 of 6	NP_001107558.1	Q9NZA1-1
CLIC5	NM_001370650.1	c.522G>A	p.Glu174Glu	synonymous	Exon 2 of 7	NP_001357579.1	Q9NZA1-1
CLIC5	NM_001370649.1	c.-55+49783G>A		intron	N/A	NP_001357578.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIC5	ENST00000185206.12	TSL:1	c.522G>A	p.Glu174Glu	synonymous	Exon 1 of 6	ENSP00000185206.6	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

GnomAD2 exomes

AF:

0.186

AC:

28979

AN:

155996

AF XY:

0.198

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 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

African (AFR)

AF:

0.0431

AC:

1362

AN:

31592

American (AMR)

AF:

0.105

AC:

3739

AN:

35692

Ashkenazi Jewish (ASJ)

AF:

0.243

AC:

6099

AN:

25122

East Asian (EAS)

AF:

0.338

AC:

12074

AN:

35724

South Asian (SAS)

AF:

0.332

AC:

26316

AN:

79190

European-Finnish (FIN)

AF:

0.151

AC:

7418

AN:

49280

Middle Eastern (MID)

AF:

0.232

AC:

1323

AN:

5692

European-Non Finnish (NFE)

AF:

0.159

AC:

171773

AN:

1078370

Other (OTH)

AF:

0.176

AC:

10221

AN:

57988

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

9797

19594

29391

39188

48985

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6352

12704

19056

25408

31760

<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:

0.140

AC:

21331

AN:

152216

Hom.:

1970

Cov.:

AF XY:

0.143

AC XY:

10676

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0518

AC:

2151

AN:

41556

American (AMR)

AF:

0.127

AC:

1943

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.235

AC:

815

AN:

3462

East Asian (EAS)

AF:

0.331

AC:

1712

AN:

5172

South Asian (SAS)

AF:

0.332

AC:

1601

AN:

4816

European-Finnish (FIN)

AF:

0.155

AC:

1642

AN:

10602

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.161

AC:

10933

AN:

68004

Other (OTH)

AF:

0.145

AC:

305

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

909

1818

2727

3636

4545

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

252

504

756

1008

1260

<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:

0.159

Hom.:

2398

Bravo

AF:

0.129

Asia WGS

AF:

0.336

AC:

1166

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

5.6

(source)

DANN

Benign

0.27

PhyloP100

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over