Genetic Variant KCNJ3:c.919+9229T>G (chr2-154719048-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002239.4(KCNJ3):c.919+9229T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 151,736 control chromosomes in the GnomAD database, including 5,748 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 0.27 ( 5748 hom., cov: 32)

Consequence

KCNJ3
NM_002239.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.375

Publications

13 publications found

Variant links:

Genes affected

KCNJ3 (HGNC:6264): (potassium inwardly rectifying channel subfamily J member 3) Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, is controlled by G-proteins and plays an important role in regulating heartbeat. It associates with three other G-protein-activated potassium channels to form a heteromultimeric pore-forming complex that also couples to neurotransmitter receptors in the brain and whereby channel activation can inhibit action potential firing by hyperpolarizing the plasma membrane. These multimeric G-protein-gated inwardly-rectifying potassium (GIRK) channels may play a role in the pathophysiology of epilepsy, addiction, Down's syndrome, ataxia, and Parkinson's disease. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, May 2012]

KCNJ3 links:

Genome browser will be placed here

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=-0.7).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ3	NM_002239.4 link	c.919+9229T>G		intron_variant	Intron 2 of 2	ENST00000295101.3	NP_002230.1
KCNJ3	NM_001260508.2 link	c.702+19571T>G		intron_variant	Intron 1 of 1		NP_001247437.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
KCNJ3	ENST00000295101.3 link	c.919+9229T>G	intron_variant	Intron 2 of 2	1	NM_002239.4	ENSP00000295101.2
KCNJ3	ENST00000544049.2 link	c.702+19571T>G	intron_variant	Intron 1 of 1	1		ENSP00000438410.1
KCNJ3	ENST00000651198.1 link	c.382+9229T>G	intron_variant	Intron 3 of 3			ENSP00000498639.1
KCNJ3	ENST00000493505.1 link	n.262+9229T>G	intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.270

AC:

40972

AN:

151618

Hom.:

5740

Cov.:

show subpopulations

Gnomad AFR

AF:

0.203

Gnomad AMI

AF:

0.455

Gnomad AMR

AF:

0.275

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.281

Gnomad SAS

AF:

0.298

Gnomad FIN

AF:

0.308

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.295

Gnomad OTH

AF:

0.273

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.270

AC:

41013

AN:

151736

Hom.:

5748

Cov.:

AF XY:

0.272

AC XY:

20137

AN XY:

74140

show subpopulations

African (AFR)

AF:

0.203

AC:

8403

AN:

41390

American (AMR)

AF:

0.275

AC:

4186

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

1202

AN:

3466

East Asian (EAS)

AF:

0.281

AC:

1442

AN:

5138

South Asian (SAS)

AF:

0.299

AC:

1441

AN:

4812

European-Finnish (FIN)

AF:

0.308

AC:

3238

AN:

10520

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.295

AC:

20036

AN:

67862

Other (OTH)

AF:

0.276

AC:

580

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1519

3038

4558

6077

7596

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

426

852

1278

1704

2130

<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:

0.281

Hom.:

18673

Bravo

AF:

0.265

Asia WGS

AF:

0.306

AC:

1064

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.89

(source)

DANN

Benign

0.84

PhyloP100

-0.38

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

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

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