ENST00000375780.6:c.-412G>A

Variant names:

• chr6-31737157-C-T
• rs378538
• ENST00000375780.6:c.-412G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 7 publications found

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]

ACMG classification

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

Selected	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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16333 AN: 151976 Hom.: 1199 Cov.: 31

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.: 5 Cov.: 3 AF XY: 0.0546 AC XY: 139 AN XY: 2544

African (AFR) AF: 0.134 AC: 11 AN: 82

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 36

East Asian (EAS) AF: 0.100 AC: 2 AN: 20

South Asian (SAS) AF: 0.0769 AC: 8 AN: 104

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 14

European-Non Finnish (NFE) AF: 0.0498 AC: 225 AN: 4516

Other (OTH) AF: 0.0381 AC: 8 AN: 210

GnomAD4 genome AF: 0.107 AC: 16334 AN: 152094 Hom.: 1198 Cov.: 31 AF XY: 0.107 AC XY: 7949 AN XY: 74382

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: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0692 AC: 4707 AN: 67972

Other (OTH) AF: 0.106 AC: 224 AN: 2106

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
DANN	Benign	0.69
PhyloP100		0.30
PromoterAI		0.0010	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs378538; hg19: chr6-31704934;