1-16024780-A-C

Variant names:

• chr1-16024780-A-C
• rs10927887
• NM_004070.4:c.247A>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.247A>C​(p.Arg83Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: CLCNKA NM_004070.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107
• Publications: 45 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=-0.87).
• BP7: Synonymous conserved (PhyloP=0.107 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004070.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLCNKA	NM_004070.4	MANE Select	c.247A>C	p.Arg83Arg	synonymous	Exon 4 of 20	NP_004061.3
	CLCNKA	NM_001042704.2		c.247A>C	p.Arg83Arg	synonymous	Exon 4 of 20	NP_001036169.1
	CLCNKA	NM_001257139.2		c.229+852A>C		intron	N/A	NP_001244068.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLCNKA	ENST00000331433.5	TSL:1 MANE Select	c.247A>C	p.Arg83Arg	synonymous	Exon 4 of 20	ENSP00000332771.4
	CLCNKA	ENST00000375692.5	TSL:1	c.247A>C	p.Arg83Arg	synonymous	Exon 5 of 21	ENSP00000364844.1
	CLCNKA	ENST00000495784.1	TSL:5	n.405A>C		non_coding_transcript_exon	Exon 4 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 60

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.2
DANN	Benign	0.61
PhyloP100		0.11
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: rs10927887; hg19: chr1-16351275;