rs378538

Positions:

• chr6-31737157-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001287593.1(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 NM_001287593.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CLIC1	NM_001287593.1	c.-412G>A		5_prime_UTR_variant	1/7		NP_001274522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLIC1	ENST00000375780.6	c.-412G>A		5_prime_UTR_variant	1/7	1		ENSP00000364935.2
CLIC1	ENST00000395892.5	c.-50-807G>A		intron_variant		3		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

Gnomad4 AFR exome AF: 0.134

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.100

Gnomad4 SAS exome AF: 0.0769

Gnomad4 NFE exome AF: 0.0498

Gnomad4 OTH exome AF: 0.0381

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

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.0697

Gnomad4 ASJ AF: 0.0522

Gnomad4 EAS AF: 0.0715

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.0688

Gnomad4 NFE AF: 0.0692

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0907 Hom.: 92

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
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs378538; hg19: chr6-31704934;