11-128890715-G-C

Variant names:

• chr11-128890715-G-C
• rs11221497
• ENST00000957736.1:c.-11+191G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000957736.1(KCNJ5):​c.-11+191G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,152 control chromosomes in the GnomAD database, including 2,952 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (2952 hom., cov: 33)
• Consequence: KCNJ5 ENST00000957736.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84
• Publications: 7 publications found

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-AS1 (HGNC:28584): (KCNJ5 antisense RNA 1) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000957736.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ5	ENST00000957736.1		c.-11+191G>C		intron	N/A	ENSP00000627795.1
	KCNJ5	ENST00000957737.1		c.-168+16G>C		intron	N/A	ENSP00000627796.1
	KCNJ5-AS1	ENST00000730925.1		n.314+13716C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29306 AN: 152034 Hom.: 2948 Cov.: 33

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.0992

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.211

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.193 AC: 29326 AN: 152152 Hom.: 2952 Cov.: 33 AF XY: 0.188 AC XY: 13970 AN XY: 74386

African (AFR) AF: 0.186 AC: 7742 AN: 41514

American (AMR) AF: 0.170 AC: 2597 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 1000 AN: 3470

East Asian (EAS) AF: 0.0997 AC: 513 AN: 5148

South Asian (SAS) AF: 0.116 AC: 561 AN: 4818

European-Finnish (FIN) AF: 0.155 AC: 1644 AN: 10616

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14506 AN: 67964

Other (OTH) AF: 0.210 AC: 443 AN: 2112

Alfa AF: 0.196 Hom.: 405

Bravo AF: 0.196

Asia WGS AF: 0.135 AC: 468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.47
DANN	Benign	0.39
PhyloP100		-1.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11221497;

hg19: chr11-128760610;