1-16022729-A-G

Variant names:

• chr1-16022729-A-G
• rs139590893
• NM_004070.4:c.100+10A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_004070.4(CLCNKA):​c.100+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00253 in 1,516,894 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0026 (5 hom.)
• Consequence: CLCNKA NM_004070.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.63
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-16022729-A-G is Benign according to our data. Variant chr1-16022729-A-G is described in ClinVar as [Benign]. Clinvar id is 718138.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 5 Unknown,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLCNKA	NM_004070.4	c.100+10A>G		intron_variant	Intron 2 of 19	ENST00000331433.5	NP_004061.3
CLCNKA	NM_001042704.2	c.100+10A>G		intron_variant	Intron 2 of 19		NP_001036169.1
CLCNKA	NM_001257139.2	c.100+10A>G		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.100+10A>G		intron_variant	Intron 2 of 19	1	NM_004070.4	ENSP00000332771.4

Frequencies

GnomAD3 genomes AF: 0.00162 AC: 247 AN: 152144 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00272

Gnomad OTH AF: 0.00384

GnomAD2 exomes AF: 0.00142 AC: 189 AN: 133470 AF XY: 0.00138

Gnomad AFR exome AF: 0.000217

Gnomad AMR exome AF: 0.00124

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000436

Gnomad NFE exome AF: 0.00277

Gnomad OTH exome AF: 0.00272

GnomAD4 exome AF: 0.00263 AC: 3595 AN: 1364632 Hom.: 5 Cov.: 28 AF XY: 0.00260 AC XY: 1745 AN XY: 670668

African (AFR) AF: 0.000384 AC: 12 AN: 31278

American (AMR) AF: 0.00116 AC: 38 AN: 32898

Ashkenazi Jewish (ASJ) AF: 0.0000876 AC: 2 AN: 22822

East Asian (EAS) AF: 0.00 AC: 0 AN: 35700

South Asian (SAS) AF: 0.0000276 AC: 2 AN: 72536

European-Finnish (FIN) AF: 0.000355 AC: 17 AN: 47862

Middle Eastern (MID) AF: 0.00310 AC: 17 AN: 5492

European-Non Finnish (NFE) AF: 0.00319 AC: 3382 AN: 1059478

Other (OTH) AF: 0.00221 AC: 125 AN: 56566

GnomAD4 genome AF: 0.00162 AC: 247 AN: 152262 Hom.: 0 Cov.: 33 AF XY: 0.00138 AC XY: 103 AN XY: 74450

African (AFR) AF: 0.000553 AC: 23 AN: 41558

American (AMR) AF: 0.00183 AC: 28 AN: 15300

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00272 AC: 185 AN: 68004

Other (OTH) AF: 0.00380 AC: 8 AN: 2108

Alfa AF: 0.00183 Hom.: 0

Bravo AF: 0.00167

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 09, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.020
DANN	Benign	0.71
PhyloP100		-1.6
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: rs139590893; hg19: chr1-16349224;