1-24771754-T-C

Variant names:

• chr1-24771754-T-C
• rs9332415
• NM_013943.3:c.73-25988T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_013943.3(CLIC4):​c.73-25988T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 392,268 control chromosomes in the GnomAD database, including 75,898 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 0.62 (30204 hom., cov: 32)
  • Exomes 𝑓: 0.61 (45694 hom.)
• Consequence: CLIC4 NM_013943.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 8 publications found

Genes affected

CLIC4 (HGNC:13518): (chloride intracellular channel 4) 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 4 (CLIC4) protein, encoded by the CLIC4 gene, is a member of the p64 family; the gene is expressed in many tissues and exhibits a intracellular vesicular pattern in Panc-1 cells (pancreatic cancer cells). [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIC4	NM_013943.3	c.73-25988T>C		intron_variant	Intron 1 of 5	ENST00000374379.9	NP_039234.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLIC4	ENST00000374379.9	c.73-25988T>C		intron_variant	Intron 1 of 5	1	NM_013943.3	ENSP00000363500.4
CLIC4	ENST00000488683.1	n.73-25988T>C		intron_variant	Intron 1 of 6	2		ENSP00000436538.1
CLIC4	ENST00000489758.1	n.218-25988T>C		intron_variant	Intron 1 of 1	2
CLIC4	ENST00000497755.1	n.245-21423T>C		intron_variant	Intron 1 of 5	3

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93921 AN: 151946 Hom.: 30201 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.732

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.631

GnomAD4 exome AF: 0.607 AC: 145708 AN: 240204 Hom.: 45694 AF XY: 0.598 AC XY: 83969 AN XY: 140510

African (AFR) AF: 0.361 AC: 2402 AN: 6646

American (AMR) AF: 0.656 AC: 12848 AN: 19594

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 3554 AN: 7108

East Asian (EAS) AF: 0.469 AC: 4190 AN: 8940

South Asian (SAS) AF: 0.467 AC: 21156 AN: 45292

European-Finnish (FIN) AF: 0.689 AC: 8965 AN: 13010

Middle Eastern (MID) AF: 0.461 AC: 1138 AN: 2468

European-Non Finnish (NFE) AF: 0.672 AC: 84697 AN: 126128

Other (OTH) AF: 0.613 AC: 6758 AN: 11018

GnomAD4 genome AF: 0.618 AC: 93944 AN: 152064 Hom.: 30204 Cov.: 32 AF XY: 0.618 AC XY: 45923 AN XY: 74336

African (AFR) AF: 0.437 AC: 18093 AN: 41446

American (AMR) AF: 0.700 AC: 10701 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2005 AN: 3462

East Asian (EAS) AF: 0.510 AC: 2641 AN: 5180

South Asian (SAS) AF: 0.525 AC: 2527 AN: 4814

European-Finnish (FIN) AF: 0.732 AC: 7741 AN: 10572

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.709 AC: 48189 AN: 67992

Other (OTH) AF: 0.631 AC: 1330 AN: 2108

Alfa AF: 0.661 Hom.: 6792

Bravo AF: 0.610

Asia WGS AF: 0.543 AC: 1889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Benign	0.90
PhyloP100		1.1
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: rs9332415; hg19: chr1-25098245;