rs400547

Positions:

• chr6-31734933-C-T

Variant summary

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

The NM_001288.6(CLIC1):​c.40-670G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 151,908 control chromosomes in the GnomAD database, including 1,191 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 (1191 hom., cov: 31)
• Consequence: CLIC1 NM_001288.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLIC1	NM_001288.6	c.40-670G>A		intron_variant		ENST00000375784.8	NP_001279.2
CLIC1	NM_001287593.1	c.40-670G>A		intron_variant			NP_001274522.1
CLIC1	NM_001287594.3	c.40-670G>A		intron_variant			NP_001274523.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLIC1	ENST00000375784.8	c.40-670G>A		intron_variant		1	NM_001288.6	ENSP00000364940.3

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16297 AN: 151790 Hom.: 1192 Cov.: 31

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0697

Gnomad ASJ AF: 0.0525

Gnomad EAS AF: 0.0711

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0682

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0694

Gnomad OTH AF: 0.106

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.107 AC: 16299 AN: 151908 Hom.: 1191 Cov.: 31 AF XY: 0.107 AC XY: 7923 AN XY: 74236

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.0695

Gnomad4 ASJ AF: 0.0525

Gnomad4 EAS AF: 0.0717

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.0682

Gnomad4 NFE AF: 0.0694

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0731 Hom.: 604

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	-0.95
CADD	Benign	1.7
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs400547; hg19: chr6-31702710;