NM_000890.5:c.938-10G>A

Variant names:

• chr11-128916399-G-A
• rs4937391
• NM_000890.5:c.938-10G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000890.5(KCNJ5):​c.938-10G>A variant causes a 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 intron
• Scores: Splicing: ADA: 0.00004011
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: -0.677

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]

ACMG classification

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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ5	NM_000890.5	c.938-10G>A		intron_variant	Intron 2 of 2	ENST00000529694.6	NP_000881.3
KCNJ5	NM_001354169.2	c.938-10G>A		intron_variant	Intron 3 of 3		NP_001341098.1
KCNJ5	XM_011542810.4	c.938-10G>A		intron_variant	Intron 2 of 2		XP_011541112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ5	ENST00000529694.6	c.938-10G>A		intron_variant	Intron 2 of 2	1	NM_000890.5	ENSP00000433295.1
KCNJ5	ENST00000338350.4	c.938-10G>A		intron_variant	Intron 3 of 3	1		ENSP00000339960.4
KCNJ5	ENST00000533599.1	c.938-10G>A		intron_variant	Intron 1 of 1	1		ENSP00000434266.1

Frequencies

GnomAD3 genomes AF: 0.743 AC: 112980 AN: 152026 Hom.: 42202 Cov.: 32

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

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.: 34 AF XY: 0.726 AC XY: 526065 AN XY: 725010

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.: 32 AF XY: 0.742 AC XY: 55187 AN XY: 74360

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:12

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:6

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 06, 2014

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Apr 04, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Familial hyperaldosteronism type III Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Long QT syndrome 13 Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Congenital long QT syndrome Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Long QT syndrome Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: 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	-0.85
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

Other links and lift over

dbSNP: rs4937391; hg19: chr11-128786294;