rs10803407

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004070.4(CLCNKA):​c.1846-6T>A variant causes a splice region, intron 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. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CLCNKA
NM_004070.4 splice_region, intron

Scores

2
Splicing: ADA: 0.001765
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0590

Publications

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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CLCNKANM_004070.4 linkc.1846-6T>A splice_region_variant, intron_variant Intron 17 of 19 ENST00000331433.5 NP_004061.3 P51800-1
CLCNKANM_001042704.2 linkc.1846-9T>A intron_variant Intron 17 of 19 NP_001036169.1 P51800-3
CLCNKANM_001257139.2 linkc.1717-6T>A splice_region_variant, intron_variant Intron 16 of 18 NP_001244068.1 P51800-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CLCNKAENST00000331433.5 linkc.1846-6T>A splice_region_variant, intron_variant Intron 17 of 19 1 NM_004070.4 ENSP00000332771.4 P51800-1
CLCNKAENST00000375692.5 linkc.1846-9T>A intron_variant Intron 18 of 20 1 ENSP00000364844.1 P51800-3
CLCNKAENST00000439316.6 linkc.1717-6T>A splice_region_variant, intron_variant Intron 16 of 18 2 ENSP00000414445.2 P51800-2
CLCNKAENST00000464764.5 linkn.2450-6T>A splice_region_variant, intron_variant Intron 21 of 23 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD2 exomes
AF:
0.00
AC:
0
AN:
250740
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
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
1458844
Hom.:
0
Cov.:
35
AF XY:
0.00
AC XY:
0
AN XY:
725852
African (AFR)
AF:
0.00
AC:
0
AN:
33448
American (AMR)
AF:
0.00
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26104
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39684
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86224
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52560
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5762
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1110040
Other (OTH)
AF:
0.00
AC:
0
AN:
60302
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
3.1
DANN
Benign
0.75
PhyloP100
-0.059
Mutation Taster
=93/7
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0018
dbscSNV1_RF
Benign
0.13
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs10803407; hg19: chr1-16358932; API