1-16023667-C-T

Variant names:

• chr1-16023667-C-T
• rs57147817
• NM_004070.4:c.101-133C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_004070.4(CLCNKA):​c.101-133C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00557 in 997,568 control chromosomes in the GnomAD database, including 183 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (108 hom., cov: 33)
  • Exomes 𝑓: 0.0027 (75 hom.)
• Consequence: CLCNKA NM_004070.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.73
• Publications: 0 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 -16 ACMG points.

• BP6: Variant 1-16023667-C-T is Benign according to our data. Variant chr1-16023667-C-T is described in ClinVar as [Benign]. Clinvar id is 1291352.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLCNKA	NM_004070.4	c.101-133C>T		intron_variant	Intron 2 of 19	ENST00000331433.5	NP_004061.3
CLCNKA	NM_001042704.2	c.101-133C>T		intron_variant	Intron 2 of 19		NP_001036169.1
CLCNKA	NM_001257139.2	c.101-133C>T		intron_variant	Intron 2 of 18		NP_001244068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLCNKA	ENST00000331433.5	c.101-133C>T		intron_variant	Intron 2 of 19	1	NM_004070.4	ENSP00000332771.4

Frequencies

GnomAD3 genomes AF: 0.0216 AC: 3282 AN: 152126 Hom.: 108 Cov.: 33

Gnomad AFR AF: 0.0739

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00929

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000515

Gnomad OTH AF: 0.0196

GnomAD4 exome AF: 0.00269 AC: 2270 AN: 845324 Hom.: 75 AF XY: 0.00222 AC XY: 973 AN XY: 437466

African (AFR) AF: 0.0752 AC: 1642 AN: 21834

American (AMR) AF: 0.00554 AC: 193 AN: 34818

Ashkenazi Jewish (ASJ) AF: 0.000142 AC: 3 AN: 21124

East Asian (EAS) AF: 0.0000617 AC: 2 AN: 32426

South Asian (SAS) AF: 0.000160 AC: 11 AN: 68624

European-Finnish (FIN) AF: 0.0000254 AC: 1 AN: 39400

Middle Eastern (MID) AF: 0.00746 AC: 24 AN: 3218

European-Non Finnish (NFE) AF: 0.000282 AC: 165 AN: 584330

Other (OTH) AF: 0.00579 AC: 229 AN: 39550

GnomAD4 genome AF: 0.0216 AC: 3286 AN: 152244 Hom.: 108 Cov.: 33 AF XY: 0.0203 AC XY: 1514 AN XY: 74426

African (AFR) AF: 0.0738 AC: 3064 AN: 41518

American (AMR) AF: 0.00928 AC: 142 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000500 AC: 34 AN: 68000

Other (OTH) AF: 0.0194 AC: 41 AN: 2116

Alfa AF: 0.0200 Hom.: 10

Bravo AF: 0.0254

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 11, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	10
DANN	Benign	0.79
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.25		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs57147817; hg19: chr1-16350162;