1-16023055-G-T

Position:

• chr1-16023055-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004070.4(CLCNKA):​c.100+336G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 152,368 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.021 (59 hom., cov: 34)
• Consequence: CLCNKA NM_004070.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.325

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=-0.91).
• BP6: Variant 1-16023055-G-T is Benign according to our data. Variant chr1-16023055-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1316530.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0214 (3260/152368) while in subpopulation NFE AF= 0.0284 (1933/68028). AF 95% confidence interval is 0.0274. There are 59 homozygotes in gnomad4. There are 1630 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 59 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCNKA	NM_004070.4	c.100+336G>T		intron_variant		ENST00000331433.5	NP_004061.3
CLCNKA	NM_001042704.2	c.100+336G>T		intron_variant			NP_001036169.1
CLCNKA	NM_001257139.2	c.100+336G>T		intron_variant			NP_001244068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCNKA	ENST00000331433.5	c.100+336G>T		intron_variant		1	NM_004070.4	ENSP00000332771	P4

Frequencies

GnomAD3 genomes AF: 0.0214 AC: 3259 AN: 152250 Hom.: 59 Cov.: 34

Gnomad AFR AF: 0.00506

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.0169

Gnomad ASJ AF: 0.0619

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0176

Gnomad FIN AF: 0.0368

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0284

Gnomad OTH AF: 0.0235

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

GnomAD4 genome AF: 0.0214 AC: 3260 AN: 152368 Hom.: 59 Cov.: 34 AF XY: 0.0219 AC XY: 1630 AN XY: 74510

Gnomad4 AFR AF: 0.00507

Gnomad4 AMR AF: 0.0167

Gnomad4 ASJ AF: 0.0619

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0178

Gnomad4 FIN AF: 0.0368

Gnomad4 NFE AF: 0.0284

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.0130 Hom.: 3

Bravo AF: 0.0195

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely 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	-0.91
CADD	Benign	2.0
DANN	Benign	0.51

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: rs111470804; hg19: chr1-16349550;