rs5218

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000525.4(KCNJ11):c.570C>T(p.Ala190Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,611,284 control chromosomes in the GnomAD database, including 72,074 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 5170 hom., cov: 33)

Exomes 𝑓: 0.29 ( 66904 hom. )

Consequence

KCNJ11
NM_000525.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.279

Variant links:

Genes affected

KCNJ11 (HGNC:6257): (potassium inwardly rectifying channel subfamily J member 11) 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. The encoded protein, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, is controlled by G-proteins and is found associated with the sulfonylurea receptor SUR. Mutations in this gene are a cause of familial persistent hyperinsulinemic hypoglycemia of infancy (PHHI), an autosomal recessive disorder characterized by unregulated insulin secretion. Defects in this gene may also contribute to autosomal dominant non-insulin-dependent diabetes mellitus type II (NIDDM), transient neonatal diabetes mellitus type 3 (TNDM3), and permanent neonatal diabetes mellitus (PNDM). Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, Oct 2009]

KCNJ11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 11-17387522-G-A is Benign according to our data. Variant chr11-17387522-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 158680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.279 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ11	NM_000525.4 link	c.570C>T	p.Ala190Ala	synonymous_variant	Exon 1 of 1	ENST00000339994.5	NP_000516.3	Q14654-1B2RC52
KCNJ11	NM_001166290.2 link	c.309C>T	p.Ala103Ala	synonymous_variant	Exon 2 of 2		NP_001159762.1	Q14654-2A0A804HHV7
KCNJ11	NM_001377296.1 link	c.309C>T	p.Ala103Ala	synonymous_variant	Exon 3 of 3		NP_001364225.1
KCNJ11	NM_001377297.1 link	c.309C>T	p.Ala103Ala	synonymous_variant	Exon 2 of 2		NP_001364226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ11	ENST00000339994.5 link	c.570C>T	p.Ala190Ala	synonymous_variant	Exon 1 of 1	6	NM_000525.4	ENSP00000345708.4		Q14654-1

Frequencies

GnomAD3 genomes

AF:

0.230

AC:

35011

AN:

152016

Hom.:

5169

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0667

Gnomad AMI

AF:

0.285

Gnomad AMR

AF:

0.185

Gnomad ASJ

AF:

0.197

Gnomad EAS

AF:

0.494

Gnomad SAS

AF:

0.167

Gnomad FIN

AF:

0.349

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.308

Gnomad OTH

AF:

0.215

GnomAD3 exomes

AF:

0.257

AC:

63365

AN:

246490

Hom.:

9487

AF XY:

0.257

AC XY:

34301

AN XY:

133488

show subpopulations

Gnomad AFR exome

AF:

0.0605

Gnomad AMR exome

AF:

0.142

Gnomad ASJ exome

AF:

0.198

Gnomad EAS exome

AF:

0.490

Gnomad SAS exome

AF:

0.164

Gnomad FIN exome

AF:

0.336

Gnomad NFE exome

AF:

0.299

Gnomad OTH exome

AF:

0.255

GnomAD4 exome

AF:

0.294

AC:

429328

AN:

1459150

Hom.:

66904

Cov.:

AF XY:

0.290

AC XY:

210455

AN XY:

725796

show subpopulations

Gnomad4 AFR exome

AF:

0.0562

Gnomad4 AMR exome

AF:

0.146

Gnomad4 ASJ exome

AF:

0.193

Gnomad4 EAS exome

AF:

0.474

Gnomad4 SAS exome

AF:

0.165

Gnomad4 FIN exome

AF:

0.335

Gnomad4 NFE exome

AF:

0.313

Gnomad4 OTH exome

AF:

0.277

GnomAD4 genome

AF:

0.230

AC:

35014

AN:

152134

Hom.:

5170

Cov.:

AF XY:

0.233

AC XY:

17302

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0666

Gnomad4 AMR

AF:

0.185

Gnomad4 ASJ

AF:

0.197

Gnomad4 EAS

AF:

0.495

Gnomad4 SAS

AF:

0.167

Gnomad4 FIN

AF:

0.349

Gnomad4 NFE

AF:

0.308

Gnomad4 OTH

AF:

0.216

Alfa

AF:

0.269

Hom.:

4313

Bravo

AF:

0.210

Asia WGS

AF:

0.292

AC:

1011

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 14871556, 29396286, 17327377, 17823772, 22916062, 22512215, 28460053, 21573802, 24018988, 1731660, 17727257, 16429405, 11310586, 26740944, 15115830, 24068186, 21765448, 25725792, 17257281, 14551916, 18290324) -

not specified

Benign:2

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hyperinsulinemic hypoglycemia, familial, 2

Benign:2

Apr 28, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Diabetes mellitus, transient neonatal, 3

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Permanent neonatal diabetes mellitus

Benign:1

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Maturity-onset diabetes of the young type 13

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

4.5

DANN

Benign

0.90

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over