NM_002239.4:c.919+39406G>A

Variant names:

• chr2-154749225-G-A
• rs2652443
• NM_002239.4:c.919+39406G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002239.4(KCNJ3):​c.919+39406G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 151,848 control chromosomes in the GnomAD database, including 8,535 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 0.31 (8535 hom., cov: 32)
• Consequence: KCNJ3 NM_002239.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ3	NM_002239.4	c.919+39406G>A		intron_variant	Intron 2 of 2	ENST00000295101.3	NP_002230.1
KCNJ3	NM_001260508.2	c.702+49748G>A		intron_variant	Intron 1 of 1		NP_001247437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ3	ENST00000295101.3	c.919+39406G>A		intron_variant	Intron 2 of 2	1	NM_002239.4	ENSP00000295101.2
KCNJ3	ENST00000544049.2	c.702+49748G>A		intron_variant	Intron 1 of 1	1		ENSP00000438410.1
KCNJ3	ENST00000651198.1	c.382+39406G>A		intron_variant	Intron 3 of 3			ENSP00000498639.1
KCNJ3	ENST00000493505.1	n.262+39406G>A		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46920 AN: 151730 Hom.: 8526 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.309 AC: 46937 AN: 151848 Hom.: 8535 Cov.: 32 AF XY: 0.312 AC XY: 23131 AN XY: 74240

African (AFR) AF: 0.117 AC: 4845 AN: 41462

American (AMR) AF: 0.444 AC: 6754 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1421 AN: 3460

East Asian (EAS) AF: 0.452 AC: 2332 AN: 5158

South Asian (SAS) AF: 0.483 AC: 2328 AN: 4820

European-Finnish (FIN) AF: 0.302 AC: 3187 AN: 10544

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.368 AC: 25002 AN: 67872

Other (OTH) AF: 0.346 AC: 729 AN: 2106

Alfa AF: 0.363 Hom.: 17477

Bravo AF: 0.308

Asia WGS AF: 0.432 AC: 1498 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.40
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2652443; hg19: chr2-155605737;