Genetic Variant KCNJ3:c.920-58882C>T (chr2-154795845-C-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_002239.4(KCNJ3):c.920-58882C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 151,790 control chromosomes in the GnomAD database, including 10,886 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 0.37 ( 10886 hom., cov: 32)

Consequence

KCNJ3
NM_002239.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0480

Publications

9 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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ3	NM_002239.4 link	c.920-58882C>T		intron_variant	Intron 2 of 2	ENST00000295101.3	NP_002230.1	P48549-1
KCNJ3	NM_001260508.2 link	c.703-58882C>T		intron_variant	Intron 1 of 1		NP_001247437.1	P48549-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
KCNJ3	ENST00000295101.3 link	c.920-58882C>T	intron_variant	Intron 2 of 2	1	NM_002239.4	ENSP00000295101.2	P48549-1
KCNJ3	ENST00000544049.2 link	c.703-58882C>T	intron_variant	Intron 1 of 1	1		ENSP00000438410.1	P48549-2
KCNJ3	ENST00000651198.1 link	c.383-58882C>T	intron_variant	Intron 3 of 3			ENSP00000498639.1	A0A494C0M7
KCNJ3	ENST00000493505.1 link	n.263-58882C>T	intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.373

AC:

56551

AN:

151670

Hom.:

10876

Cov.:

show subpopulations

Gnomad AFR

AF:

0.436

Gnomad AMI

AF:

0.200

Gnomad AMR

AF:

0.438

Gnomad ASJ

AF:

0.336

Gnomad EAS

AF:

0.515

Gnomad SAS

AF:

0.367

Gnomad FIN

AF:

0.379

Gnomad MID

AF:

0.287

Gnomad NFE

AF:

0.313

Gnomad OTH

AF:

0.368

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

GnomAD4 genome

AF:

0.373

AC:

56593

AN:

151790

Hom.:

10886

Cov.:

AF XY:

0.379

AC XY:

28095

AN XY:

74162

show subpopulations

African (AFR)

AF:

0.436

AC:

18040

AN:

41400

American (AMR)

AF:

0.438

AC:

6663

AN:

15216

Ashkenazi Jewish (ASJ)

AF:

0.336

AC:

1168

AN:

3472

East Asian (EAS)

AF:

0.515

AC:

2646

AN:

5138

South Asian (SAS)

AF:

0.365

AC:

1760

AN:

4822

European-Finnish (FIN)

AF:

0.379

AC:

3986

AN:

10512

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.313

AC:

21279

AN:

67914

Other (OTH)

AF:

0.371

AC:

783

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1780

3559

5339

7118

8898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

542

1084

1626

2168

2710

<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:

0.331

Hom.:

14277

Bravo

AF:

0.381

Asia WGS

AF:

0.441

AC:

1535

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.2

(source)

DANN

Benign

0.73

PhyloP100

-0.048

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over