11-128912217-C-T

Variant names:

• chr11-128912217-C-T
• rs45516097
• NM_000890.5:c.937+7C>T

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.937+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0195 in 1,597,078 control chromosomes in the GnomAD database, including 1,633 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.061 (712 hom., cov: 33)
  • Exomes 𝑓: 0.015 (921 hom.)
• Consequence: KCNJ5 NM_000890.5 splice_region, intron
• Scores: Splicing: ADA: 0.00006703
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.761

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=-0.82).
• BP6: Variant 11-128912217-C-T is Benign according to our data. Variant chr11-128912217-C-T is described in ClinVar as [Benign]. Clinvar id is 137994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-128912217-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ5	NM_000890.5	c.937+7C>T		splice_region_variant, intron_variant	Intron 2 of 2	ENST00000529694.6	NP_000881.3
KCNJ5	NM_001354169.2	c.937+7C>T		splice_region_variant, intron_variant	Intron 3 of 3		NP_001341098.1
KCNJ5	XM_011542810.4	c.937+7C>T		splice_region_variant, 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.937+7C>T		splice_region_variant, intron_variant	Intron 2 of 2	1	NM_000890.5	ENSP00000433295.1
KCNJ5	ENST00000338350.4	c.937+7C>T		splice_region_variant, intron_variant	Intron 3 of 3	1		ENSP00000339960.4
KCNJ5	ENST00000533599.1	c.937+7C>T		splice_region_variant, intron_variant	Intron 1 of 1	1		ENSP00000434266.1

Frequencies

GnomAD3 genomes AF: 0.0610 AC: 9283 AN: 152154 Hom.: 710 Cov.: 33

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0415

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.0896

Gnomad SAS AF: 0.0127

Gnomad FIN AF: 0.00499

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00814

Gnomad OTH AF: 0.0602

GnomAD3 exomes AF: 0.0299 AC: 7012 AN: 234546 Hom.: 361 AF XY: 0.0255 AC XY: 3258 AN XY: 127940

Gnomad AFR exome AF: 0.183

Gnomad AMR exome AF: 0.0220

Gnomad ASJ exome AF: 0.0153

Gnomad EAS exome AF: 0.0907

Gnomad SAS exome AF: 0.00798

Gnomad FIN exome AF: 0.00692

Gnomad NFE exome AF: 0.0101

Gnomad OTH exome AF: 0.0280

GnomAD4 exome AF: 0.0151 AC: 21806 AN: 1444806 Hom.: 921 Cov.: 35 AF XY: 0.0143 AC XY: 10302 AN XY: 719400

Gnomad4 AFR exome AF: 0.186

Gnomad4 AMR exome AF: 0.0249

Gnomad4 ASJ exome AF: 0.0149

Gnomad4 EAS exome AF: 0.0756

Gnomad4 SAS exome AF: 0.00843

Gnomad4 FIN exome AF: 0.00659

Gnomad4 NFE exome AF: 0.00715

Gnomad4 OTH exome AF: 0.0329

GnomAD4 genome AF: 0.0611 AC: 9300 AN: 152272 Hom.: 712 Cov.: 33 AF XY: 0.0592 AC XY: 4411 AN XY: 74448

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.0413

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.0898

Gnomad4 SAS AF: 0.0127

Gnomad4 FIN AF: 0.00499

Gnomad4 NFE AF: 0.00814

Gnomad4 OTH AF: 0.0601

Alfa AF: 0.0314 Hom.: 61

Bravo AF: 0.0706

EpiCase AF: 0.00856

EpiControl AF: 0.0100

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

-

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Apr 10, 2023

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 16, 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

- -

Familial hyperaldosteronism type III Benign:1

Jan 12, 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. -

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	-0.82
CADD	Benign	0.82
DANN	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000067
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.010		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: rs45516097; hg19: chr11-128782112;