Genetic Variant CLIC1:c.-217C>A (chr6-31736517-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001288.6(CLIC1):c.-217C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,381,240 control chromosomes in the GnomAD database, including 9,487 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.077 ( 560 hom., cov: 31)

Exomes 𝑓: 0.11 ( 8927 hom. )

Consequence

CLIC1
NM_001288.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.729

Publications

42 publications found

Variant links:

Genes affected

CLIC1 (HGNC:2062): (chloride intracellular channel 1) Chloride channels are a diverse group of proteins that regulate fundamental cellular processes including stabilization of cell membrane potential, transepithelial transport, maintenance of intracellular pH, and regulation of cell volume. Chloride intracellular channel 1 is a member of the p64 family; the protein localizes principally to the cell nucleus and exhibits both nuclear and plasma membrane chloride ion channel activity. [provided by RefSeq, Jul 2008]

CLIC1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CLIC1	NM_001288.6 link	c.-217C>A	5_prime_UTR_variant	Exon 1 of 6	ENST00000375784.8	NP_001279.2	O00299Q5SRT3
CLIC1	NM_001287594.3 link	c.-85C>A	5_prime_UTR_variant	Exon 1 of 7		NP_001274523.1	O00299Q5SRT3Q53FB0
CLIC1	NM_001287593.1 link	c.-50-167C>A	intron_variant	Intron 1 of 6		NP_001274522.1	O00299Q5SRT3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLIC1	ENST00000375784.8 link	c.-217C>A		5_prime_UTR_variant	Exon 1 of 6	1	NM_001288.6	ENSP00000364940.3		O00299

Frequencies

GnomAD3 genomes

AF:

0.0766

AC:

11645

AN:

152016

Hom.:

560

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0626

Gnomad AMI

AF:

0.0691

Gnomad AMR

AF:

0.0373

Gnomad ASJ

AF:

0.0398

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0788

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.0594

GnomAD4 exome

AF:

0.110

AC:

135746

AN:

1229106

Hom.:

8927

Cov.:

AF XY:

0.108

AC XY:

64040

AN XY:

593032

show subpopulations

African (AFR)

AF:

0.0651

AC:

1749

AN:

26858

American (AMR)

AF:

0.0286

AC:

503

AN:

17568

Ashkenazi Jewish (ASJ)

AF:

0.0425

AC:

745

AN:

17550

East Asian (EAS)

AF:

0.0000941

AC:

AN:

31868

South Asian (SAS)

AF:

0.00280

AC:

152

AN:

54208

European-Finnish (FIN)

AF:

0.0830

AC:

2309

AN:

27834

Middle Eastern (MID)

AF:

0.00913

AC:

AN:

3396

European-Non Finnish (NFE)

AF:

0.126

AC:

125457

AN:

999096

Other (OTH)

AF:

0.0946

AC:

4797

AN:

50728

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

6036

12072

18107

24143

30179

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0766

AC:

11646

AN:

152134

Hom.:

560

Cov.:

AF XY:

0.0712

AC XY:

5297

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0625

AC:

2595

AN:

41506

American (AMR)

AF:

0.0372

AC:

569

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0398

AC:

138

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00145

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0788

AC:

834

AN:

10582

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.108

AC:

7309

AN:

67968

Other (OTH)

AF:

0.0588

AC:

124

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

536

1073

1609

2146

2682

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.100

Hom.:

2400

Bravo

AF:

0.0733

Asia WGS

AF:

0.00837

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.8

(source)

DANN

Benign

0.68

PhyloP100

-0.73

PromoterAI

-0.058

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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6-31736517-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over