rs4937391

Variant summary

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

The NM_000890.5(KCNJ5):c.938-10G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 1,608,824 control chromosomes in the GnomAD database, including 423,607 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 42221 hom., cov: 32)

Exomes 𝑓: 0.72 ( 381386 hom. )

Consequence

KCNJ5
NM_000890.5 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00004011

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.677

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 11-128916399-G-A is Benign according to our data. Variant chr11-128916399-G-A is described in ClinVar as [Benign]. Clinvar id is 137995.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-128916399-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
KCNJ5	NM_000890.5 linkuse as main transcript	c.938-10G>A	splice_polypyrimidine_tract_variant, intron_variant	ENST00000529694.6
KCNJ5	NM_001354169.2 linkuse as main transcript	c.938-10G>A	splice_polypyrimidine_tract_variant, intron_variant
KCNJ5	XM_011542810.4 linkuse as main transcript	c.938-10G>A	splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
KCNJ5	ENST00000529694.6 linkuse as main transcript	c.938-10G>A	splice_polypyrimidine_tract_variant, intron_variant	1	NM_000890.5	P1
KCNJ5	ENST00000338350.4 linkuse as main transcript	c.938-10G>A	splice_polypyrimidine_tract_variant, intron_variant	1		P1
KCNJ5	ENST00000533599.1 linkuse as main transcript	c.938-10G>A	splice_polypyrimidine_tract_variant, intron_variant	1		P1

Frequencies

GnomAD3 genomes

AF:

0.743

AC:

112980

AN:

152026

Hom.:

42202

Cov.:

show subpopulations

Gnomad AFR

AF:

0.791

Gnomad AMI

AF:

0.794

Gnomad AMR

AF:

0.743

Gnomad ASJ

AF:

0.754

Gnomad EAS

AF:

0.660

Gnomad SAS

AF:

0.772

Gnomad FIN

AF:

0.682

Gnomad MID

AF:

0.759

Gnomad NFE

AF:

0.726

Gnomad OTH

AF:

0.771

GnomAD3 exomes

AF:

0.731

AC:

183011

AN:

250316

Hom.:

67038

AF XY:

0.734

AC XY:

99343

AN XY:

135400

show subpopulations

Gnomad AFR exome

AF:

0.794

Gnomad AMR exome

AF:

0.710

Gnomad ASJ exome

AF:

0.763

Gnomad EAS exome

AF:

0.664

Gnomad SAS exome

AF:

0.780

Gnomad FIN exome

AF:

0.684

Gnomad NFE exome

AF:

0.732

Gnomad OTH exome

AF:

0.745

GnomAD4 exome

AF:

0.723

AC:

1052544

AN:

1456680

Hom.:

381386

Cov.:

AF XY:

0.726

AC XY:

526065

AN XY:

725010

show subpopulations

Gnomad4 AFR exome

AF:

0.800

Gnomad4 AMR exome

AF:

0.710

Gnomad4 ASJ exome

AF:

0.763

Gnomad4 EAS exome

AF:

0.669

Gnomad4 SAS exome

AF:

0.778

Gnomad4 FIN exome

AF:

0.684

Gnomad4 NFE exome

AF:

0.718

Gnomad4 OTH exome

AF:

0.730

GnomAD4 genome

AF:

0.743

AC:

113049

AN:

152144

Hom.:

42221

Cov.:

AF XY:

0.742

AC XY:

55187

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.791

Gnomad4 AMR

AF:

0.743

Gnomad4 ASJ

AF:

0.754

Gnomad4 EAS

AF:

0.660

Gnomad4 SAS

AF:

0.772

Gnomad4 FIN

AF:

0.682

Gnomad4 NFE

AF:

0.726

Gnomad4 OTH

AF:

0.772

Alfa

AF:

0.738

Hom.:

19456

Bravo

AF:

0.747

Asia WGS

AF:

0.746

AC:

2590

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

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	Clinical Genetics, Academic Medical Center	-	- -
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, criteria provided, single submitter	clinical testing	GeneDx	Jan 06, 2014	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. -

Familial hyperaldosteronism type III

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -
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. -

Long QT syndrome 13

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

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

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

Cadd

Benign

3.6

Dann

Benign

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000040

dbscSNV1_RF

Benign

0.0020

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