Genetic Variant KCNJ5:c.-11+8742G>T (chr11-128900463-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000890.5(KCNJ5):c.-11+8742G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0844 in 152,162 control chromosomes in the GnomAD database, including 1,113 homozygotes. 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 0.084 ( 1113 hom., cov: 33)

Exomes 𝑓: 0.071 ( 0 hom. )

Consequence

KCNJ5
NM_000890.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.296

Publications

5 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000890.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KCNJ5	NM_000890.5	MANE Select	c.-11+8742G>T	intron	N/A	NP_000881.3
KCNJ5	NM_001354169.2		c.-100+8742G>T	intron	N/A	NP_001341098.1	P48544
KCNJ5-AS1	NR_045767.1		n.2660C>A	non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KCNJ5	ENST00000529694.6	TSL:1 MANE Select	c.-11+8742G>T	intron	N/A	ENSP00000433295.1	P48544
KCNJ5	ENST00000338350.4	TSL:1	c.-100+8742G>T	intron	N/A	ENSP00000339960.4	P48544
KCNJ5-AS1	ENST00000310799.9	TSL:1	n.2726C>A	non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes

AF:

0.0845

AC:

12842

AN:

152030

Hom.:

1115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.165

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.138

Gnomad ASJ

AF:

0.0225

Gnomad EAS

AF:

0.242

Gnomad SAS

AF:

0.234

Gnomad FIN

AF:

0.0453

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0115

Gnomad OTH

AF:

0.0786

GnomAD4 exome

AF:

0.0714

AC:

AN:

Hom.:

Cov.:

AF XY:

0.125

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0845

AC:

12849

AN:

152148

Hom.:

1113

Cov.:

AF XY:

0.0900

AC XY:

6698

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.165

AC:

6839

AN:

41474

American (AMR)

AF:

0.139

AC:

2123

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0225

AC:

AN:

3470

East Asian (EAS)

AF:

0.241

AC:

1248

AN:

5170

South Asian (SAS)

AF:

0.233

AC:

1121

AN:

4820

European-Finnish (FIN)

AF:

0.0453

AC:

480

AN:

10592

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0115

AC:

784

AN:

68020

Other (OTH)

AF:

0.0806

AC:

170

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

523

1046

1569

2092

2615

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

146

292

438

584

730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0414

Hom.:

717

Bravo

AF:

0.0933

Asia WGS

AF:

0.247

AC:

857

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.8

(source)

DANN

Benign

0.67

PhyloP100

0.30

Mutation Taster

=100/0

polymorphism (auto)

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over