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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001288.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CLIC1	NM_001288.6	MANE Select	c.-217C>A	5_prime_UTR	Exon 1 of 6	NP_001279.2
CLIC1	NM_001287594.3		c.-85C>A	5_prime_UTR	Exon 1 of 7	NP_001274523.1	O00299
CLIC1	NM_001287593.1		c.-50-167C>A	intron	N/A	NP_001274522.1	O00299

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CLIC1	ENST00000375784.8	TSL:1 MANE Select	c.-217C>A	5_prime_UTR	Exon 1 of 6	ENSP00000364940.3	O00299
CLIC1	ENST00000375780.6	TSL:1	c.-50-167C>A	intron	N/A	ENSP00000364935.2	O00299
CLIC1	ENST00000616760.1	TSL:2	c.-85C>A	5_prime_UTR	Exon 1 of 7	ENSP00000479808.1	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

Age Distribution

Exome Het

Exome Hom

Variant carriers

4930

9860

14790

19720

24650

<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:

0.0766

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

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

248

372

496

620

<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:

0.100

Hom.:

2400

Bravo

AF:

0.0733

Asia WGS

AF:

0.00837

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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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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