11-128912083-T-G

Position:

chr11-128912083-T-G

Variant summary

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

The ENST00000529694.6(KCNJ5):c.810T>G(p.Leu270=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 1,613,502 control chromosomes in the GnomAD database, including 549,350 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L270L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.84 ( 54355 hom., cov: 33)

Exomes 𝑓: 0.82 ( 494995 hom. )

Consequence

KCNJ5
ENST00000529694.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:15

Conservation

PhyloP100: 1.91

Variant links:

Genes affected

KCNJ5 (HGNC:6266): (potassium inwardly rectifying channel subfamily J member 5) This gene encodes an integral membrane protein which belongs to one of seven subfamilies of inward-rectifier potassium channel proteins called potassium channel subfamily J. The encoded protein is a subunit of the potassium channel which is homotetrameric. It is controlled by G-proteins and has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Naturally occurring mutations in this gene are associated with aldosterone-producing adenomas. [provided by RefSeq, Aug 2017]

KCNJ5 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=-0.56).

BP6

Variant 11-128912083-T-G is Benign according to our data. Variant chr11-128912083-T-G is described in ClinVar as [Benign]. Clinvar id is 137991.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-128912083-T-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.91 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KCNJ5	NM_000890.5 linkuse as main transcript	c.810T>G	p.Leu270=	synonymous_variant	2/3	ENST00000529694.6	NP_000881.3
KCNJ5	NM_001354169.2 linkuse as main transcript	c.810T>G	p.Leu270=	synonymous_variant	3/4		NP_001341098.1
KCNJ5	XM_011542810.4 linkuse as main transcript	c.810T>G	p.Leu270=	synonymous_variant	2/3		XP_011541112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
KCNJ5	ENST00000529694.6 linkuse as main transcript	c.810T>G	p.Leu270=	synonymous_variant	2/3	1	NM_000890.5	ENSP00000433295	P1
KCNJ5	ENST00000338350.4 linkuse as main transcript	c.810T>G	p.Leu270=	synonymous_variant	3/4	1		ENSP00000339960	P1
KCNJ5	ENST00000533599.1 linkuse as main transcript	c.810T>G	p.Leu270=	synonymous_variant	1/2	1		ENSP00000434266	P1

Frequencies

GnomAD3 genomes

AF:

0.844

AC:

128333

AN:

152036

Hom.:

54311

Cov.:

show subpopulations

Gnomad AFR

AF:

0.892

Gnomad AMI

AF:

0.865

Gnomad AMR

AF:

0.836

Gnomad ASJ

AF:

0.841

Gnomad EAS

AF:

0.879

Gnomad SAS

AF:

0.893

Gnomad FIN

AF:

0.795

Gnomad MID

AF:

0.826

Gnomad NFE

AF:

0.818

Gnomad OTH

AF:

0.857

GnomAD3 exomes

AF:

0.838

AC:

209044

AN:

249344

Hom.:

87814

AF XY:

0.842

AC XY:

113562

AN XY:

134866

show subpopulations

Gnomad AFR exome

AF:

0.895

Gnomad AMR exome

AF:

0.814

Gnomad ASJ exome

AF:

0.848

Gnomad EAS exome

AF:

0.880

Gnomad SAS exome

AF:

0.892

Gnomad FIN exome

AF:

0.793

Gnomad NFE exome

AF:

0.825

Gnomad OTH exome

AF:

0.836

GnomAD4 exome

AF:

0.822

AC:

1201864

AN:

1461348

Hom.:

494995

Cov.:

AF XY:

0.826

AC XY:

600315

AN XY:

726966

show subpopulations

Gnomad4 AFR exome

AF:

0.899

Gnomad4 AMR exome

AF:

0.813

Gnomad4 ASJ exome

AF:

0.847

Gnomad4 EAS exome

AF:

0.872

Gnomad4 SAS exome

AF:

0.890

Gnomad4 FIN exome

AF:

0.789

Gnomad4 NFE exome

AF:

0.814

Gnomad4 OTH exome

AF:

0.828

GnomAD4 genome

AF:

0.844

AC:

128431

AN:

152154

Hom.:

54355

Cov.:

AF XY:

0.845

AC XY:

62859

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.892

Gnomad4 AMR

AF:

0.836

Gnomad4 ASJ

AF:

0.841

Gnomad4 EAS

AF:

0.879

Gnomad4 SAS

AF:

0.893

Gnomad4 FIN

AF:

0.795

Gnomad4 NFE

AF:

0.818

Gnomad4 OTH

AF:

0.856

Alfa

AF:

0.829

Hom.:

63600

Bravo

AF:

0.848

Asia WGS

AF:

0.883

AC:

3066

AN:

3476

EpiCase

AF:

0.833

EpiControl

AF:

0.833

ClinVar

Significance: Benign

Submissions summary: Benign:15

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 04, 2023	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Familial hyperaldosteronism type III

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -

Long QT syndrome 13

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Long QT syndrome 13;C3838758:Familial hyperaldosteronism type III

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Mar 03, 2022

- -

Congenital long QT syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Long QT syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 12, 2015

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

4.6

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