11-128891397-GACACACACACACACACACACACACACACACACAC-GACACACACACACACACACACACAC

Variant names:

• chr11-128891397-GACACACACAC-G
• rs113761140
• NM_000890.5:c.-299_-290delCACACACACA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000890.5(KCNJ5):​c.-299_-290delCACACACACA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.026 (65 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNJ5 NM_000890.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197
• Publications: 2 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ5	NM_000890.5	c.-299_-290delCACACACACA		5_prime_UTR_variant	Exon 1 of 3	ENST00000529694.6	NP_000881.3
KCNJ5	NM_001354169.2	c.-388_-379delCACACACACA		5_prime_UTR_variant	Exon 1 of 4		NP_001341098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ5	ENST00000529694.6	c.-299_-290delCACACACACA		5_prime_UTR_variant	Exon 1 of 3	1	NM_000890.5	ENSP00000433295.1
KCNJ5-AS1	ENST00000730925.1	n.314+13024_314+13033delGTGTGTGTGT		intron_variant	Intron 2 of 2
KCNJ5-AS1	ENST00000730926.1	n.285+13024_285+13033delGTGTGTGTGT		intron_variant	Intron 2 of 2
KCNJ5	ENST00000338350.4	c.-423_-414delACACACACAC		upstream_gene_variant		1		ENSP00000339960.4

Frequencies

GnomAD3 genomes AF: 0.0258 AC: 2179 AN: 84614 Hom.: 66 Cov.: 0

Gnomad AFR AF: 0.0389

Gnomad AMI AF: 0.0188

Gnomad AMR AF: 0.0642

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.0575

Gnomad SAS AF: 0.0122

Gnomad FIN AF: 0.00177

Gnomad MID AF: 0.0932

Gnomad NFE AF: 0.0140

Gnomad OTH AF: 0.0371

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1044 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 794

African (AFR) AF: 0.00 AC: 0 AN: 14

American (AMR) AF: 0.00 AC: 0 AN: 12

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6

East Asian (EAS) AF: 0.00 AC: 0 AN: 40

South Asian (SAS) AF: 0.00 AC: 0 AN: 36

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 872

Other (OTH) AF: 0.00 AC: 0 AN: 52

GnomAD4 genome AF: 0.0258 AC: 2183 AN: 84618 Hom.: 65 Cov.: 0 AF XY: 0.0261 AC XY: 1007 AN XY: 38620

African (AFR) AF: 0.0390 AC: 744 AN: 19084

American (AMR) AF: 0.0647 AC: 491 AN: 7592

Ashkenazi Jewish (ASJ) AF: 0.0274 AC: 64 AN: 2338

East Asian (EAS) AF: 0.0571 AC: 154 AN: 2698

South Asian (SAS) AF: 0.0123 AC: 24 AN: 1958

European-Finnish (FIN) AF: 0.00177 AC: 6 AN: 3382

Middle Eastern (MID) AF: 0.0877 AC: 10 AN: 114

European-Non Finnish (NFE) AF: 0.0140 AC: 640 AN: 45836

Other (OTH) AF: 0.0369 AC: 40 AN: 1084

Alfa AF: 0.00 Hom.: 58

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.20
Mutation Taster		=300/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs113761140; hg19: chr11-128761292;