6-31736517-G-T

Position:

• chr6-31736517-G-T

Variant summary

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

The NM_001288.6(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 NM_001288.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.729

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLIC1	NM_001288.6	c.-217C>A		5_prime_UTR_variant	1/6	ENST00000375784.8	NP_001279.2
CLIC1	NM_001287594.3	c.-85C>A		5_prime_UTR_variant	1/7		NP_001274523.1
CLIC1	NM_001287593.1	c.-50-167C>A		intron_variant			NP_001274522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLIC1	ENST00000375784.8	c.-217C>A		5_prime_UTR_variant	1/6	1	NM_001288.6	ENSP00000364940.3

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

Gnomad4 AFR exome AF: 0.0651

Gnomad4 AMR exome AF: 0.0286

Gnomad4 ASJ exome AF: 0.0425

Gnomad4 EAS exome AF: 0.0000941

Gnomad4 SAS exome AF: 0.00280

Gnomad4 FIN exome AF: 0.0830

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.0946

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

Gnomad4 AFR AF: 0.0625

Gnomad4 AMR AF: 0.0372

Gnomad4 ASJ AF: 0.0398

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.0788

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.0588

Alfa AF: 0.0948 Hom.: 1116

Bravo AF: 0.0733

Asia WGS AF: 0.00837 AC: 30 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.8
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs3131383; hg19: chr6-31704294;