chr2-154753126-C-T

Variant names:

• chr2-154753126-C-T
• rs1992701
• NM_002239.4:c.919+43307C>T

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+43307C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 151,724 control chromosomes in the GnomAD database, including 17,082 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 0.46 (17082 hom., cov: 32)
• Consequence: KCNJ3 NM_002239.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.325
• Publications: 3 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 (EAS) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002239.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ3	NM_002239.4	MANE Select	c.919+43307C>T		intron	N/A	NP_002230.1	P48549-1
	KCNJ3	NM_001260508.2		c.702+53649C>T		intron	N/A	NP_001247437.1	P48549-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ3	ENST00000295101.3	TSL:1 MANE Select	c.919+43307C>T		intron	N/A	ENSP00000295101.2	P48549-1
	KCNJ3	ENST00000544049.2	TSL:1	c.702+53649C>T		intron	N/A	ENSP00000438410.1	P48549-2
	KCNJ3	ENST00000651198.1		c.382+43307C>T		intron	N/A	ENSP00000498639.1	A0A494C0M7

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69537 AN: 151606 Hom.: 17059 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.875

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.459 AC: 69595 AN: 151724 Hom.: 17082 Cov.: 32 AF XY: 0.466 AC XY: 34529 AN XY: 74114

African (AFR) AF: 0.307 AC: 12717 AN: 41414

American (AMR) AF: 0.568 AC: 8659 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1745 AN: 3468

East Asian (EAS) AF: 0.875 AC: 4519 AN: 5164

South Asian (SAS) AF: 0.645 AC: 3097 AN: 4804

European-Finnish (FIN) AF: 0.486 AC: 5105 AN: 10510

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.475 AC: 32217 AN: 67816

Other (OTH) AF: 0.487 AC: 1026 AN: 2108

Alfa AF: 0.467 Hom.: 10620

Bravo AF: 0.456

Asia WGS AF: 0.700 AC: 2421 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.76
PhyloP100		-0.33
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: rs1992701; hg19: chr2-155609638;