dbSNP rs378538: CLIC1:c.-412G>A (chr6-31737157-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000375780.6(CLIC1):c.-412G>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 0.106 in 157,080 control chromosomes in the GnomAD database, including 1,203 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 0.11 ( 1198 hom., cov: 31)

Exomes 𝑓: 0.051 ( 5 hom. )

Consequence

CLIC1
ENST00000375780.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.305

Publications

7 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:

Genome browser will be placed here

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=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIC1	NM_001287593.1 link	c.-412G>A		5_prime_UTR_variant	Exon 1 of 7		NP_001274522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLIC1	ENST00000375780.6 link	c.-412G>A		5_prime_UTR_variant	Exon 1 of 7	1		ENSP00000364935.2
CLIC1	ENST00000395892.5 link	c.-50-807G>A		intron_variant	Intron 2 of 7	3		ENSP00000379229.1

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16333

AN:

151976

Hom.:

1199

Cov.:

show subpopulations

Gnomad AFR

AF:

0.204

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.0700

Gnomad ASJ

AF:

0.0522

Gnomad EAS

AF:

0.0709

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.0688

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0692

Gnomad OTH

AF:

0.107

GnomAD4 exome

AF:

0.0509

AC:

254

AN:

4986

Hom.:

Cov.:

AF XY:

0.0546

AC XY:

139

AN XY:

2544

show subpopulations

African (AFR)

AF:

0.134

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.100

AC:

AN:

South Asian (SAS)

AF:

0.0769

AC:

AN:

104

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0498

AC:

225

AN:

4516

Other (OTH)

AF:

0.0381

AC:

AN:

210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.107

AC:

16334

AN:

152094

Hom.:

1198

Cov.:

AF XY:

0.107

AC XY:

7949

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.203

AC:

8425

AN:

41472

American (AMR)

AF:

0.0697

AC:

1066

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0522

AC:

181

AN:

3470

East Asian (EAS)

AF:

0.0715

AC:

369

AN:

5164

South Asian (SAS)

AF:

0.115

AC:

556

AN:

4826

European-Finnish (FIN)

AF:

0.0688

AC:

729

AN:

10592

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0692

AC:

4707

AN:

67972

Other (OTH)

AF:

0.106

AC:

224

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

670

1339

2009

2678

3348

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

352

528

704

880

<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:

0.0955

Hom.:

104

Bravo

AF:

0.112

Asia WGS

AF:

0.0760

AC:

263

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

4.1

(source)

DANN

Benign

0.69

PhyloP100

0.30

PromoterAI

0.0010

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over