6-31736517-G-T

Variant names:

• chr6-31736517-G-T
• rs3131383
• NM_001288.6:c.-217C>A

Variant summary

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

The ENST00000375784.8(CLIC1):​c.-217C>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 0.107 in 1,381,240 control chromosomes in the GnomAD database, including 9,487 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 0.077 (560 hom., cov: 31)
  • Exomes 𝑓: 0.11 (8927 hom.)
• Consequence: CLIC1 ENST00000375784.8 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.729
• Publications: 42 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000375784.8. 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_001288.6	MANE Select	c.-217C>A		5_prime_UTR	Exon 1 of 6	NP_001279.2
	CLIC1	NM_001287594.3		c.-85C>A		5_prime_UTR	Exon 1 of 7	NP_001274523.1
	CLIC1	NM_001287593.1		c.-50-167C>A		intron	N/A	NP_001274522.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIC1	ENST00000375784.8	TSL:1 MANE Select	c.-217C>A		5_prime_UTR	Exon 1 of 6	ENSP00000364940.3
	CLIC1	ENST00000375780.6	TSL:1	c.-50-167C>A		intron	N/A	ENSP00000364935.2
	CLIC1	ENST00000616760.1	TSL:2	c.-85C>A		5_prime_UTR	Exon 1 of 7	ENSP00000479808.1

Frequencies

GnomAD3 genomes AF: 0.0766 AC: 11645 AN: 152016 Hom.: 560 Cov.: 31

Gnomad AFR AF: 0.0626

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0373

Gnomad ASJ AF: 0.0398

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0788

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0594

GnomAD4 exome AF: 0.110 AC: 135746 AN: 1229106 Hom.: 8927 Cov.: 31 AF XY: 0.108 AC XY: 64040 AN XY: 593032

African (AFR) AF: 0.0651 AC: 1749 AN: 26858

American (AMR) AF: 0.0286 AC: 503 AN: 17568

Ashkenazi Jewish (ASJ) AF: 0.0425 AC: 745 AN: 17550

East Asian (EAS) AF: 0.0000941 AC: 3 AN: 31868

South Asian (SAS) AF: 0.00280 AC: 152 AN: 54208

European-Finnish (FIN) AF: 0.0830 AC: 2309 AN: 27834

Middle Eastern (MID) AF: 0.00913 AC: 31 AN: 3396

European-Non Finnish (NFE) AF: 0.126 AC: 125457 AN: 999096

Other (OTH) AF: 0.0946 AC: 4797 AN: 50728

GnomAD4 genome AF: 0.0766 AC: 11646 AN: 152134 Hom.: 560 Cov.: 31 AF XY: 0.0712 AC XY: 5297 AN XY: 74382

African (AFR) AF: 0.0625 AC: 2595 AN: 41506

American (AMR) AF: 0.0372 AC: 569 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0398 AC: 138 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4822

European-Finnish (FIN) AF: 0.0788 AC: 834 AN: 10582

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7309 AN: 67968

Other (OTH) AF: 0.0588 AC: 124 AN: 2110

Alfa AF: 0.100 Hom.: 2400

Bravo AF: 0.0733

Asia WGS AF: 0.00837 AC: 30 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.8
DANN	Benign	0.68
PhyloP100		-0.73
PromoterAI		-0.058	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs3131383; hg19: chr6-31704294;