chr11-128891431-C-A

Variant names:

• chr11-128891431-C-A
• rs868416561
• NM_000890.5:c.-301C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000890.5(KCNJ5):​c.-301C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.000022 (0 hom., cov: 18)
• Consequence: KCNJ5 NM_000890.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.88
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.19).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ5	NM_000890.5	c.-301C>A		5_prime_UTR_variant	Exon 1 of 3	ENST00000529694.6	NP_000881.3
KCNJ5	NM_001354169.2	c.-390C>A		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.-301C>A		5_prime_UTR_variant	Exon 1 of 3	1	NM_000890.5	ENSP00000433295.1
KCNJ5-AS1	ENST00000730925.1	n.314+13000G>T		intron_variant	Intron 2 of 2
KCNJ5-AS1	ENST00000730926.1	n.285+13000G>T		intron_variant	Intron 2 of 2
KCNJ5	ENST00000338350.4	c.-390C>A		upstream_gene_variant		1		ENSP00000339960.4

Frequencies

GnomAD3 genomes AF: 0.0000217 AC: 2 AN: 92174 Hom.: 0 Cov.: 18

Gnomad AFR AF: 0.0000951

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000217 AC: 2 AN: 92174 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 43880

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000951 AC: 2 AN: 21032

American (AMR) AF: 0.00 AC: 0 AN: 9360

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2210

East Asian (EAS) AF: 0.00 AC: 0 AN: 2654

South Asian (SAS) AF: 0.00 AC: 0 AN: 2322

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6098

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 182

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 46706

Other (OTH) AF: 0.00 AC: 0 AN: 1134

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.044843), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.2
CADD	Benign	2.3
DANN	Benign	0.51
PhyloP100		-4.9
PromoterAI		0.099	Neutral

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: rs868416561; hg19: chr11-128761326;