NM_002239.4:c.919+12448A>G

Variant names:

• chr2-154722267-A-G
• rs3106651
• NM_002239.4:c.919+12448A>G

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+12448A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 151,978 control chromosomes in the GnomAD database, including 17,220 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 0.47 (17220 hom., cov: 31)
• Consequence: KCNJ3 NM_002239.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.172
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) 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	c.919+12448A>G		intron_variant	Intron 2 of 2	ENST00000295101.3	NP_002230.1
KCNJ3	NM_001260508.2	c.702+22790A>G		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+12448A>G		intron_variant	Intron 2 of 2	1	NM_002239.4	ENSP00000295101.2
KCNJ3	ENST00000544049.2	c.702+22790A>G		intron_variant	Intron 1 of 1	1		ENSP00000438410.1
KCNJ3	ENST00000651198.1	c.382+12448A>G		intron_variant	Intron 3 of 3			ENSP00000498639.1
KCNJ3	ENST00000493505.1	n.262+12448A>G		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71693 AN: 151858 Hom.: 17186 Cov.: 31

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.472 AC: 71774 AN: 151978 Hom.: 17220 Cov.: 31 AF XY: 0.471 AC XY: 34973 AN XY: 74284

African (AFR) AF: 0.505 AC: 20926 AN: 41422

American (AMR) AF: 0.404 AC: 6165 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1506 AN: 3466

East Asian (EAS) AF: 0.360 AC: 1857 AN: 5162

South Asian (SAS) AF: 0.438 AC: 2108 AN: 4812

European-Finnish (FIN) AF: 0.536 AC: 5667 AN: 10566

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.470 AC: 31925 AN: 67962

Other (OTH) AF: 0.447 AC: 942 AN: 2108

Alfa AF: 0.466 Hom.: 8781

Bravo AF: 0.464

Asia WGS AF: 0.438 AC: 1521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.0
DANN	Benign	0.37
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: rs3106651; hg19: chr2-155578779;