rs1010069

Variant names:

• chr1-16026442-G-A
• rs1010069
• NM_004070.4:c.499-94G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-16026442-G-A
• chr1-16026442-G-C
• chr1-16026442-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004070.4(CLCNKA):​c.499-94G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 1,551,842 control chromosomes in the GnomAD database, including 177,589 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (20589 hom., cov: 31)
  • Exomes 𝑓: 0.47 (157000 hom.)
• Consequence: CLCNKA NM_004070.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.754
• Publications: 24 publications found

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 Gene-Disease associations (from GenCC):

• Bartter disease type 4B

  Inheritance: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, G2P
• Bartter syndrome type 4

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-16026442-G-A is Benign according to our data. Variant chr1-16026442-G-A is described in ClinVar as Benign. ClinVar VariationId is 1278622.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLCNKA	NM_004070.4	c.499-94G>A		intron_variant	Intron 5 of 19	ENST00000331433.5	NP_004061.3
CLCNKA	NM_001042704.2	c.499-94G>A		intron_variant	Intron 5 of 19		NP_001036169.1
CLCNKA	NM_001257139.2	c.370-94G>A		intron_variant	Intron 4 of 18		NP_001244068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLCNKA	ENST00000331433.5	c.499-94G>A		intron_variant	Intron 5 of 19	1	NM_004070.4	ENSP00000332771.4

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77369 AN: 151816 Hom.: 20571 Cov.: 31

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.523

GnomAD4 exome AF: 0.469 AC: 656313 AN: 1399908 Hom.: 157000 Cov.: 26 AF XY: 0.470 AC XY: 328191 AN XY: 697724

African (AFR) AF: 0.653 AC: 21196 AN: 32448

American (AMR) AF: 0.355 AC: 14662 AN: 41270

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 10847 AN: 25436

East Asian (EAS) AF: 0.731 AC: 28321 AN: 38768

South Asian (SAS) AF: 0.508 AC: 42516 AN: 83654

European-Finnish (FIN) AF: 0.399 AC: 20380 AN: 51134

Middle Eastern (MID) AF: 0.504 AC: 2858 AN: 5676

European-Non Finnish (NFE) AF: 0.458 AC: 486972 AN: 1063306

Other (OTH) AF: 0.491 AC: 28561 AN: 58216

GnomAD4 genome AF: 0.510 AC: 77417 AN: 151934 Hom.: 20589 Cov.: 31 AF XY: 0.505 AC XY: 37466 AN XY: 74246

African (AFR) AF: 0.637 AC: 26394 AN: 41446

American (AMR) AF: 0.409 AC: 6250 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1431 AN: 3464

East Asian (EAS) AF: 0.776 AC: 3984 AN: 5134

South Asian (SAS) AF: 0.527 AC: 2546 AN: 4828

European-Finnish (FIN) AF: 0.391 AC: 4125 AN: 10554

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 31097 AN: 67918

Other (OTH) AF: 0.523 AC: 1103 AN: 2110

Alfa AF: 0.471 Hom.: 34284

Bravo AF: 0.515

Asia WGS AF: 0.598 AC: 2077 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.0
DANN	Benign	0.70
PhyloP100		0.75
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: rs1010069; hg19: chr1-16352937; COSMIC: COSV58890920; COSMIC: COSV58890920;