rs5210

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000525.4(KCNJ11):c.*215C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 568,352 control chromosomes in the GnomAD database, including 46,171 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 15056 hom., cov: 33)

Exomes 𝑓: 0.38 ( 31115 hom. )

Consequence

KCNJ11
NM_000525.4 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.608

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 11-17386704-G-A is Benign according to our data. Variant chr11-17386704-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 303727.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
KCNJ11	NM_000525.4 linkuse as main transcript	c.*215C>T	3_prime_UTR_variant	1/1	ENST00000339994.5
KCNJ11	NM_001166290.2 linkuse as main transcript	c.*215C>T	3_prime_UTR_variant	2/2
KCNJ11	NM_001377296.1 linkuse as main transcript	c.*215C>T	3_prime_UTR_variant	3/3
KCNJ11	NM_001377297.1 linkuse as main transcript	c.*215C>T	3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ11	ENST00000339994.5 linkuse as main transcript	c.*215C>T		3_prime_UTR_variant	1/1		NM_000525.4	P1	Q14654-1

Frequencies

GnomAD3 genomes

AF:

0.433

AC:

65822

AN:

151918

Hom.:

15020

Cov.:

show subpopulations

Gnomad AFR

AF:

0.570

Gnomad AMI

AF:

0.302

Gnomad AMR

AF:

0.391

Gnomad ASJ

AF:

0.300

Gnomad EAS

AF:

0.559

Gnomad SAS

AF:

0.359

Gnomad FIN

AF:

0.367

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.376

Gnomad OTH

AF:

0.399

GnomAD4 exome

AF:

0.379

AC:

157914

AN:

416316

Hom.:

31115

Cov.:

AF XY:

0.376

AC XY:

81769

AN XY:

217688

show subpopulations

Gnomad4 AFR exome

AF:

0.566

Gnomad4 AMR exome

AF:

0.358

Gnomad4 ASJ exome

AF:

0.288

Gnomad4 EAS exome

AF:

0.524

Gnomad4 SAS exome

AF:

0.339

Gnomad4 FIN exome

AF:

0.355

Gnomad4 NFE exome

AF:

0.368

Gnomad4 OTH exome

AF:

0.387

GnomAD4 genome

AF:

0.434

AC:

65921

AN:

152036

Hom.:

15056

Cov.:

AF XY:

0.436

AC XY:

32379

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.570

Gnomad4 AMR

AF:

0.391

Gnomad4 ASJ

AF:

0.300

Gnomad4 EAS

AF:

0.560

Gnomad4 SAS

AF:

0.359

Gnomad4 FIN

AF:

0.367

Gnomad4 NFE

AF:

0.376

Gnomad4 OTH

AF:

0.402

Alfa

AF:

0.291

Hom.:

882

Bravo

AF:

0.436

Asia WGS

AF:

0.485

AC:

1688

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Type 2 diabetes mellitus

Benign:1

Benign, criteria provided, single submitter

research

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

Mutations in KCNJ11 gene can cause decreased production and secretion of insulin. This can lead to MODY which is responsive to oral sulfonylureas. rs5210 variant of KCNJ11 is associated with increased T2D risk. -

Diabetes mellitus, transient neonatal, 3

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

Hyperinsulinemic hypoglycemia, familial, 2

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

Maturity-onset diabetes of the young type 13

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.70

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