rs1889785

Positions:

• chr1-16022234-G-A
• chr1-16022234-G-C
• chr1-16022234-G-T

Variant summary

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

The NM_004070.4(CLCNKA):​c.-8+171G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 151,828 control chromosomes in the GnomAD database, including 18,904 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 0.49 (18904 hom., cov: 31)
• Consequence: CLCNKA NM_004070.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.251

Genes affected

CLCNKA (HGNC:2026): (chloride voltage-gated channel Ka) This gene is a member of the CLC family of voltage-gated chloride channels. The encoded protein is predicted to have 12 transmembrane domains, and requires a beta subunit called barttin to form a functional channel. It is thought to function in salt reabsorption in the kidney and potassium recycling in the inner ear. The gene is highly similar to CLCNKB, which is located 10 kb downstream from this gene. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

CLCNKA (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCNKA	NM_004070.4	c.-8+171G>A		intron_variant		ENST00000331433.5	NP_004061.3
CLCNKA	NM_001042704.2	c.-8+171G>A		intron_variant			NP_001036169.1
CLCNKA	NM_001257139.2	c.-8+171G>A		intron_variant			NP_001244068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCNKA	ENST00000331433.5	c.-8+171G>A		intron_variant		1	NM_004070.4	ENSP00000332771.4

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74538 AN: 151708 Hom.: 18883 Cov.: 31

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.515

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

GnomAD4 genome AF: 0.491 AC: 74587 AN: 151828 Hom.: 18904 Cov.: 31 AF XY: 0.487 AC XY: 36125 AN XY: 74184

Gnomad4 AFR AF: 0.574

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.777

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.515

Alfa AF: 0.471 Hom.: 13166

Bravo AF: 0.495

Asia WGS AF: 0.594 AC: 2064 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.8
DANN	Benign	0.64

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: rs1889785; hg19: chr1-16348729; COSMIC: COSV58890897; COSMIC: COSV58890897;