Genetic Variant KCNJ5:c.-291_-290dupCA (chr11-128891397-G-GAC) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The NM_000890.5(KCNJ5):c.-291_-290dupCA 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 0.024 ( 70 hom., cov: 3)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KCNJ5
NM_000890.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.388

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ5	NM_000890.5 link	c.-291_-290dupCA		5_prime_UTR_variant	Exon 1 of 3	ENST00000529694.6	NP_000881.3	P48544A0A5J6E2W8
KCNJ5	NM_001354169.2 link	c.-380_-379dupCA		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.-291_-290dupCA	5_prime_UTR_variant	Exon 1 of 3	1	NM_000890.5	ENSP00000433295.1	P48544
KCNJ5-AS1	ENST00000730925.1 link	n.314+13032_314+13033dupGT	intron_variant	Intron 2 of 2
KCNJ5-AS1	ENST00000730926.1 link	n.285+13032_285+13033dupGT	intron_variant	Intron 2 of 2
KCNJ5	ENST00000338350.4 link	c.-424_-423insAC	upstream_gene_variant		1		ENSP00000339960.4	P48544

Frequencies

GnomAD3 genomes

AF:

0.0236

AC:

2002

AN:

84698

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00586

Gnomad AMI

AF:

0.0434

Gnomad AMR

AF:

0.0251

Gnomad ASJ

AF:

0.0243

Gnomad EAS

AF:

0.0611

Gnomad SAS

AF:

0.0122

Gnomad FIN

AF:

0.0486

Gnomad MID

AF:

0.0169

Gnomad NFE

AF:

0.0270

Gnomad OTH

AF:

0.0213

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1044

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

794

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:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

872

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.0237

AC:

2004

AN:

84702

Hom.:

Cov.:

AF XY:

0.0235

AC XY:

909

AN XY:

38638

show subpopulations

African (AFR)

AF:

0.00585

AC:

112

AN:

19140

American (AMR)

AF:

0.0251

AC:

191

AN:

7602

Ashkenazi Jewish (ASJ)

AF:

0.0243

AC:

AN:

2344

East Asian (EAS)

AF:

0.0618

AC:

167

AN:

2702

South Asian (SAS)

AF:

0.0123

AC:

AN:

1956

European-Finnish (FIN)

AF:

0.0486

AC:

164

AN:

3374

Middle Eastern (MID)

AF:

0.0175

AC:

AN:

114

European-Non Finnish (NFE)

AF:

0.0271

AC:

1241

AN:

45854

Other (OTH)

AF:

0.0212

AC:

AN:

1086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

144

216

288

360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0232

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.39

Mutation Taster

=300/0

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

11-128891397-GACACACACACACACACACACACACACACACACAC-GACACACACACACACACACACACACACACACACACAC

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