rs12439

chr1-24843143-A-Gchr1-24843143-A-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CLIC4	NM_013943.3	c.*2206A>G		3_prime_UTR_variant	6/6	ENST00000374379.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLIC4	ENST00000374379.9	c.*2206A>G		3_prime_UTR_variant	6/6	1	NM_013943.3	P1
CLIC4	ENST00000488683.1	c.*1650+556A>G		intron_variant, NMD_transcript_variant		2

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

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

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.493

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.338

Alfa AF: 0.296 Hom.: 11240

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

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: rs12439; hg19: chr1-25169634;