dbSNP rs57147817: CLCNKA:c.101-133C>T (chr1-16023667-C-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.73

Publications

0 publications found

Variant links:

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

CLCNKA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 VariationId 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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CLCNKA	NM_004070.4	MANE Select	c.101-133C>T	intron	N/A	NP_004061.3
CLCNKA	NM_001042704.2		c.101-133C>T	intron	N/A	NP_001036169.1	P51800-3
CLCNKA	NM_001257139.2		c.101-133C>T	intron	N/A	NP_001244068.1	P51800-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CLCNKA	ENST00000331433.5	TSL:1 MANE Select	c.101-133C>T	intron	N/A	ENSP00000332771.4	P51800-1
CLCNKA	ENST00000375692.5	TSL:1	c.101-133C>T	intron	N/A	ENSP00000364844.1	P51800-3
CLCNKA	ENST00000861487.1		c.101-133C>T	intron	N/A	ENSP00000531546.1

Frequencies

GnomAD3 genomes

AF:

0.0216

AC:

3282

AN:

152126

Hom.:

108

Cov.:

show subpopulations

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.:

AF XY:

0.00222

AC XY:

973

AN XY:

437466

show subpopulations

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:

AN:

21124

East Asian (EAS)

AF:

0.0000617

AC:

AN:

32426

South Asian (SAS)

AF:

0.000160

AC:

AN:

68624

European-Finnish (FIN)

AF:

0.0000254

AC:

AN:

39400

Middle Eastern (MID)

AF:

0.00746

AC:

AN:

3218

European-Non Finnish (NFE)

AF:

0.000282

AC:

165

AN:

584330

Other (OTH)

AF:

0.00579

AC:

229

AN:

39550

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

106

213

319

426

532

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0216

AC:

3286

AN:

152244

Hom.:

108

Cov.:

AF XY:

0.0203

AC XY:

1514

AN XY:

74426

show subpopulations

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:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000415

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000500

AC:

AN:

68000

Other (OTH)

AF:

0.0194

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

144

289

433

578

722

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0200

Hom.:

Bravo

AF:

0.0254

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

-2.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over