Genetic Variant KCNJ5:c.-293_-290delCACA (chr11-128891397-GACAC-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_000890.5(KCNJ5):c.-293_-290delCACA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0407 in 85,296 control chromosomes in the GnomAD database, including 129 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.041 ( 128 hom., cov: 3)

Exomes 𝑓: 0.0048 ( 1 hom. )

Consequence

KCNJ5
NM_000890.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.151

Publications

2 publications found

Variant links:

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 links:

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

KCNJ5-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0411 (3465/84252) while in subpopulation AFR AF = 0.0491 (933/19002). AF 95% confidence interval is 0.0465. There are 128 homozygotes in GnomAd4. There are 1516 alleles in the male GnomAd4 subpopulation. Median coverage is 3. This position passed quality control check.

BS2

High AC in GnomAd4 at 3465 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ5	NM_000890.5 link	c.-293_-290delCACA		5_prime_UTR_variant	Exon 1 of 3	ENST00000529694.6	NP_000881.3	P48544A0A5J6E2W8
KCNJ5	NM_001354169.2 link	c.-382_-379delCACA		5_prime_UTR_variant	Exon 1 of 4		NP_001341098.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
KCNJ5	ENST00000529694.6 link	c.-293_-290delCACA	5_prime_UTR_variant	Exon 1 of 3	1	NM_000890.5	ENSP00000433295.1	P48544
KCNJ5-AS1	ENST00000730925.1 link	n.314+13030_314+13033delGTGT	intron_variant	Intron 2 of 2
KCNJ5-AS1	ENST00000730926.1 link	n.285+13030_285+13033delGTGT	intron_variant	Intron 2 of 2
KCNJ5	ENST00000338350.4 link	c.-423_-420delACAC	upstream_gene_variant		1		ENSP00000339960.4	P48544

Frequencies

GnomAD3 genomes

AF:

0.0411

AC:

3463

AN:

84248

Hom.:

127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0491

Gnomad AMI

AF:

0.0189

Gnomad AMR

AF:

0.0339

Gnomad ASJ

AF:

0.0287

Gnomad EAS

AF:

0.00919

Gnomad SAS

AF:

0.0319

Gnomad FIN

AF:

0.0396

Gnomad MID

AF:

0.0424

Gnomad NFE

AF:

0.0424

Gnomad OTH

AF:

0.0371

GnomAD4 exome

AF:

0.00479

AC:

AN:

1044

Hom.:

AF XY:

0.00378

AC XY:

AN XY:

794

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.0278

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00459

AC:

AN:

872

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0411

AC:

3465

AN:

84252

Hom.:

128

Cov.:

AF XY:

0.0394

AC XY:

1516

AN XY:

38440

show subpopulations

African (AFR)

AF:

0.0491

AC:

933

AN:

19002

American (AMR)

AF:

0.0337

AC:

255

AN:

7562

Ashkenazi Jewish (ASJ)

AF:

0.0287

AC:

AN:

2332

East Asian (EAS)

AF:

0.00925

AC:

AN:

2704

South Asian (SAS)

AF:

0.0327

AC:

AN:

1958

European-Finnish (FIN)

AF:

0.0396

AC:

133

AN:

3360

Middle Eastern (MID)

AF:

0.0439

AC:

AN:

114

European-Non Finnish (NFE)

AF:

0.0424

AC:

1933

AN:

45606

Other (OTH)

AF:

0.0369

AC:

AN:

1084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

110

219

329

438

548

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0567

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.15

Mutation Taster

=300/0

polymorphism

(source)

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

Publications

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11-128891397-GACACACACACACACACACACACACACACACACAC-GACACACACACACACACACACACACACACAC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over