rs371202740

Variant names:

• chr1-16033649-T-A
• rs371202740
• NM_004070.4:c.2055T>A

Your query was ambiguous. Multiple possible variants found:

• chr1-16033649-T-A
• chr1-16033649-T-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_004070.4(CLCNKA):​c.2055T>A​(p.Ala685Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000229 in 1,310,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A685A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: CLCNKA NM_004070.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.574
• Publications: 2 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP7: Synonymous conserved (PhyloP=-0.574 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLCNKA	NM_004070.4	c.2055T>A	p.Ala685Ala	synonymous_variant	Exon 20 of 20	ENST00000331433.5	NP_004061.3
CLCNKA	NM_001042704.2	c.2052T>A	p.Ala684Ala	synonymous_variant	Exon 20 of 20		NP_001036169.1
CLCNKA	NM_001257139.2	c.1926T>A	p.Ala642Ala	synonymous_variant	Exon 19 of 19		NP_001244068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLCNKA	ENST00000331433.5	c.2055T>A	p.Ala685Ala	synonymous_variant	Exon 20 of 20	1	NM_004070.4	ENSP00000332771.4
CLCNKA	ENST00000375692.5	c.2052T>A	p.Ala684Ala	synonymous_variant	Exon 21 of 21	1		ENSP00000364844.1
CLCNKA	ENST00000439316.6	c.1926T>A	p.Ala642Ala	synonymous_variant	Exon 19 of 19	2		ENSP00000414445.2
CLCNKA	ENST00000464764.5	n.2659T>A		non_coding_transcript_exon_variant	Exon 24 of 24	2

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD2 exomes AF: 0.00000442 AC: 1 AN: 226374 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000229 AC: 3 AN: 1310198 Hom.: 0 Cov.: 41 AF XY: 0.00000154 AC XY: 1 AN XY: 650322

African (AFR) AF: 0.00 AC: 0 AN: 29782

American (AMR) AF: 0.00 AC: 0 AN: 39640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19974

East Asian (EAS) AF: 0.00 AC: 0 AN: 23754

South Asian (SAS) AF: 0.0000237 AC: 2 AN: 84472

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4916

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1014748

Other (OTH) AF: 0.0000198 AC: 1 AN: 50578

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	4.3
DANN	Benign	0.66
PhyloP100		-0.57
Mutation Taster		=100/0	polymorphism

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: rs371202740; hg19: chr1-16360144;