2-154748620-C-T

Variant names:

• chr2-154748620-C-T
• rs1823002
• NM_002239.4:c.919+38801C>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+38801C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 151,922 control chromosomes in the GnomAD database, including 49,903 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 0.81 (49903 hom., cov: 32)
• Consequence: KCNJ3 NM_002239.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ3	NM_002239.4	c.919+38801C>T		intron_variant	Intron 2 of 2	ENST00000295101.3	NP_002230.1
KCNJ3	NM_001260508.2	c.702+49143C>T		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+38801C>T		intron_variant	Intron 2 of 2	1	NM_002239.4	ENSP00000295101.2
KCNJ3	ENST00000544049.2	c.702+49143C>T		intron_variant	Intron 1 of 1	1		ENSP00000438410.1
KCNJ3	ENST00000651198.1	c.382+38801C>T		intron_variant	Intron 3 of 3			ENSP00000498639.1
KCNJ3	ENST00000493505.1	n.262+38801C>T		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122598 AN: 151804 Hom.: 49867 Cov.: 32

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.849

Gnomad AMR AF: 0.840

Gnomad ASJ AF: 0.841

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.809

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.804

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

GnomAD4 genome AF: 0.808 AC: 122692 AN: 151922 Hom.: 49903 Cov.: 32 AF XY: 0.805 AC XY: 59753 AN XY: 74272

African (AFR) AF: 0.732 AC: 30354 AN: 41442

American (AMR) AF: 0.840 AC: 12776 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.841 AC: 2918 AN: 3468

East Asian (EAS) AF: 0.584 AC: 3004 AN: 5140

South Asian (SAS) AF: 0.809 AC: 3897 AN: 4820

European-Finnish (FIN) AF: 0.831 AC: 8792 AN: 10578

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.857 AC: 58253 AN: 67944

Other (OTH) AF: 0.806 AC: 1701 AN: 2110

Alfa AF: 0.844 Hom.: 57257

Bravo AF: 0.803

Asia WGS AF: 0.718 AC: 2498 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.83
DANN	Benign	0.74
PhyloP100		-0.39
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: rs1823002; hg19: chr2-155605132;