1-24808513-C-T

Variant names:

• chr1-24808513-C-T
• rs4306080
• NM_013943.3:c.183-5581C>T

Variant summary

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

The NM_013943.3(CLIC4):​c.183-5581C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 151,004 control chromosomes in the GnomAD database, including 8,909 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 0.34 (8909 hom., cov: 28)
• Consequence: CLIC4 NM_013943.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.25
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIC4	NM_013943.3	c.183-5581C>T		intron_variant	Intron 2 of 5	ENST00000374379.9	NP_039234.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLIC4	ENST00000374379.9	c.183-5581C>T		intron_variant	Intron 2 of 5	1	NM_013943.3	ENSP00000363500.4
CLIC4	ENST00000488683.1	n.183-5581C>T		intron_variant	Intron 2 of 6	2		ENSP00000436538.1
CLIC4	ENST00000497755.1	n.392-5581C>T		intron_variant	Intron 3 of 5	3

Frequencies

GnomAD3 genomes AF: 0.336 AC: 50645 AN: 150882 Hom.: 8909 Cov.: 28

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.336 AC: 50666 AN: 151004 Hom.: 8909 Cov.: 28 AF XY: 0.337 AC XY: 24821 AN XY: 73708

African (AFR) AF: 0.403 AC: 16566 AN: 41106

American (AMR) AF: 0.280 AC: 4240 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1453 AN: 3462

East Asian (EAS) AF: 0.493 AC: 2509 AN: 5094

South Asian (SAS) AF: 0.474 AC: 2248 AN: 4740

European-Finnish (FIN) AF: 0.268 AC: 2789 AN: 10406

Middle Eastern (MID) AF: 0.510 AC: 149 AN: 292

European-Non Finnish (NFE) AF: 0.290 AC: 19680 AN: 67748

Other (OTH) AF: 0.337 AC: 707 AN: 2098

Alfa AF: 0.318 Hom.: 3521

Bravo AF: 0.336

Asia WGS AF: 0.437 AC: 1520 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.47
DANN	Benign	0.64
PhyloP100		-2.3
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: rs4306080; hg19: chr1-25135004;