chr1-16022965-T-C

Position:

• chr1-16022965-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004070.4(CLCNKA):​c.100+246T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 152,196 control chromosomes in the GnomAD database, including 37,633 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.70 (37633 hom., cov: 34)
• Consequence: CLCNKA NM_004070.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0700

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 1-16022965-T-C is Benign according to our data. Variant chr1-16022965-T-C is described in ClinVar as [Benign]. Clinvar id is 1291597.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCNKA	NM_004070.4	c.100+246T>C		intron_variant		ENST00000331433.5	NP_004061.3
CLCNKA	NM_001042704.2	c.100+246T>C		intron_variant			NP_001036169.1
CLCNKA	NM_001257139.2	c.100+246T>C		intron_variant			NP_001244068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCNKA	ENST00000331433.5	c.100+246T>C		intron_variant		1	NM_004070.4	ENSP00000332771	P4

Frequencies

GnomAD3 genomes AF: 0.700 AC: 106428 AN: 152078 Hom.: 37608 Cov.: 34

Gnomad AFR AF: 0.741

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.975

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.713

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

GnomAD4 genome AF: 0.700 AC: 106504 AN: 152196 Hom.: 37633 Cov.: 34 AF XY: 0.699 AC XY: 51974 AN XY: 74396

Gnomad4 AFR AF: 0.741

Gnomad4 AMR AF: 0.643

Gnomad4 ASJ AF: 0.600

Gnomad4 EAS AF: 0.974

Gnomad4 SAS AF: 0.640

Gnomad4 FIN AF: 0.710

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.712

Alfa AF: 0.689 Hom.: 4247

Bravo AF: 0.697

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.4
DANN	Benign	0.60

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: rs9442214; hg19: chr1-16349460;