Genetic Variant ENST00000375780.6: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:

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new If you want to explore the variant's impact on the transcript ENST00000375780.6, 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000375780.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIC1	NM_001287593.1		c.-412G>A		5_prime_UTR	Exon 1 of 7	NP_001274522.1	O00299

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CLIC1	ENST00000375780.6	TSL:1	c.-412G>A	5_prime_UTR	Exon 1 of 7	ENSP00000364935.2	O00299
CLIC1	ENST00000395892.5	TSL:3	c.-50-807G>A	intron	N/A	ENSP00000379229.1	O00299
CLIC1	ENST00000864995.1		c.-112-745G>A	intron	N/A	ENSP00000535054.1

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 v4.9

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

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