NM_000890.5:c.-291_-290delCA

Variant names:

• chr11-128891397-GAC-G
• rs113761140
• NM_000890.5:c.-291_-290delCA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_000890.5(KCNJ5):​c.-291_-290delCA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0248 in 85,518 control chromosomes in the GnomAD database, including 36 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.025 (36 hom., cov: 3)
  • Exomes 𝑓: 0.00096 (0 hom.)
• Consequence: KCNJ5 NM_000890.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.388
• 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.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0251 (2119/84474) while in subpopulation AFR AF = 0.0338 (643/19032). AF 95% confidence interval is 0.0316. There are 36 homozygotes in GnomAd4. There are 979 alleles in the male GnomAd4 subpopulation. Median coverage is 3. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2119 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ5	NM_000890.5	c.-291_-290delCA		5_prime_UTR_variant	Exon 1 of 3	ENST00000529694.6	NP_000881.3
KCNJ5	NM_001354169.2	c.-380_-379delCA		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.-291_-290delCA		5_prime_UTR_variant	Exon 1 of 3	1	NM_000890.5	ENSP00000433295.1
KCNJ5-AS1	ENST00000730925.1	n.314+13032_314+13033delGT		intron_variant	Intron 2 of 2
KCNJ5-AS1	ENST00000730926.1	n.285+13032_285+13033delGT		intron_variant	Intron 2 of 2
KCNJ5	ENST00000338350.4	c.-423_-422delAC		upstream_gene_variant		1		ENSP00000339960.4

Frequencies

GnomAD3 genomes AF: 0.0251 AC: 2116 AN: 84470 Hom.: 36 Cov.: 3

Gnomad AFR AF: 0.0336

Gnomad AMI AF: 0.00188

Gnomad AMR AF: 0.0188

Gnomad ASJ AF: 0.0244

Gnomad EAS AF: 0.0232

Gnomad SAS AF: 0.0168

Gnomad FIN AF: 0.0454

Gnomad MID AF: 0.0254

Gnomad NFE AF: 0.0219

Gnomad OTH AF: 0.0187

GnomAD4 exome AF: 0.000958 AC: 1 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: 0.00115 AC: 1 AN: 872

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

GnomAD4 genome AF: 0.0251 AC: 2119 AN: 84474 Hom.: 36 Cov.: 3 AF XY: 0.0254 AC XY: 979 AN XY: 38536

African (AFR) AF: 0.0338 AC: 643 AN: 19032

American (AMR) AF: 0.0188 AC: 143 AN: 7592

Ashkenazi Jewish (ASJ) AF: 0.0244 AC: 57 AN: 2332

East Asian (EAS) AF: 0.0230 AC: 62 AN: 2700

South Asian (SAS) AF: 0.0169 AC: 33 AN: 1954

European-Finnish (FIN) AF: 0.0454 AC: 153 AN: 3372

Middle Eastern (MID) AF: 0.0263 AC: 3 AN: 114

European-Non Finnish (NFE) AF: 0.0219 AC: 1004 AN: 45772

Other (OTH) AF: 0.0186 AC: 20 AN: 1074

Alfa AF: 0.0330 Hom.: 58

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.39
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs113761140; hg19: chr11-128761292;