Genetic Variant KCNJ1:c.*499_*501dupCAA (chr11-128838623-C-CTTG) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_153766.3(KCNJ1):c.*499_*501dupCAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 160,464 control chromosomes in the GnomAD database, including 2,142 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.16 ( 2033 hom., cov: 29)

Exomes 𝑓: 0.13 ( 109 hom. )

Consequence

KCNJ1
NM_153766.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.49

Publications

2 publications found

Variant links:

Genes affected

KCNJ1 (HGNC:6255): (potassium inwardly rectifying channel subfamily J member 1) Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. It is activated by internal ATP and probably plays an important role in potassium homeostasis. The encoded protein has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Mutations in this gene have been associated with antenatal Bartter syndrome, which is characterized by salt wasting, hypokalemic alkalosis, hypercalciuria, and low blood pressure. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

KCNJ1 Gene-Disease associations (from GenCC):

Bartter disease type 2
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
antenatal Bartter syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

KCNJ1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ1	NM_153766.3 link	c.499_501dupCAA		3_prime_UTR_variant	Exon 3 of 3	ENST00000392666.6	NP_722450.1	P48048-2A0A024R3K6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ1	ENST00000392666.6 link	c.499_501dupCAA		3_prime_UTR_variant	Exon 3 of 3	1	NM_153766.3	ENSP00000376434.1		P48048-2

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24429

AN:

151958

Hom.:

2025

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.0998

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.139

Gnomad EAS

AF:

0.102

Gnomad SAS

AF:

0.301

Gnomad FIN

AF:

0.198

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.151

Gnomad OTH

AF:

0.148

GnomAD4 exome

AF:

0.127

AC:

1067

AN:

8388

Hom.:

109

Cov.:

AF XY:

0.131

AC XY:

593

AN XY:

4514

show subpopulations

African (AFR)

AF:

0.176

AC:

AN:

American (AMR)

AF:

0.0729

AC:

AN:

1194

Ashkenazi Jewish (ASJ)

AF:

0.0577

AC:

AN:

East Asian (EAS)

AF:

0.0424

AC:

AN:

236

South Asian (SAS)

AF:

0.251

AC:

208

AN:

828

European-Finnish (FIN)

AF:

0.0721

AC:

AN:

208

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.125

AC:

680

AN:

5428

Other (OTH)

AF:

0.148

AC:

AN:

392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

127

170

212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.161

AC:

24457

AN:

152076

Hom.:

2033

Cov.:

AF XY:

0.164

AC XY:

12156

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.185

AC:

7669

AN:

41492

American (AMR)

AF:

0.101

AC:

1549

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.139

AC:

481

AN:

3468

East Asian (EAS)

AF:

0.102

AC:

528

AN:

5170

South Asian (SAS)

AF:

0.302

AC:

1455

AN:

4810

European-Finnish (FIN)

AF:

0.198

AC:

2089

AN:

10566

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.151

AC:

10242

AN:

67970

Other (OTH)

AF:

0.149

AC:

314

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1049

2098

3147

4196

5245

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.153

Hom.:

176

Asia WGS

AF:

0.188

AC:

653

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Antenatal Bartter syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr11-128838623-C-CTTG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over