rs12439

Variant names:

• chr1-24843143-A-G
• rs12439
• NM_013943.3:c.*2206A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-24843143-A-G
• chr1-24843143-A-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.*2206A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 152,062 control chromosomes in the GnomAD database, including 8,910 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 (8910 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: CLIC4 NM_013943.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.876
• Publications: 23 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIC4	NM_013943.3	c.*2206A>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000374379.9	NP_039234.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLIC4	ENST00000374379.9	c.*2206A>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_013943.3	ENSP00000363500.4
CLIC4	ENST00000488683.1	n.*1650+556A>G		intron_variant	Intron 6 of 6	2		ENSP00000436538.1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50966 AN: 151942 Hom.: 8910 Cov.: 32

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.337

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.335 AC: 50989 AN: 152062 Hom.: 8910 Cov.: 32 AF XY: 0.336 AC XY: 24976 AN XY: 74344

African (AFR) AF: 0.406 AC: 16830 AN: 41454

American (AMR) AF: 0.280 AC: 4276 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1452 AN: 3468

East Asian (EAS) AF: 0.493 AC: 2552 AN: 5178

South Asian (SAS) AF: 0.438 AC: 2114 AN: 4828

European-Finnish (FIN) AF: 0.268 AC: 2838 AN: 10582

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.290 AC: 19731 AN: 67950

Other (OTH) AF: 0.338 AC: 715 AN: 2116

Alfa AF: 0.303 Hom.: 27818

Bravo AF: 0.337

Asia WGS AF: 0.426 AC: 1479 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.067
DANN	Benign	0.45
PhyloP100		-0.88
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: rs12439; hg19: chr1-25169634;