2-154719048-T-G

Variant names:

• chr2-154719048-T-G
• rs3106653
• NM_002239.4:c.919+9229T>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+9229T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 151,736 control chromosomes in the GnomAD database, including 5,748 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 0.27 (5748 hom., cov: 32)
• Consequence: KCNJ3 NM_002239.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.375
• Publications: 13 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=-0.7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.292 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+9229T>G		intron	N/A	NP_002230.1	P48549-1
	KCNJ3	NM_001260508.2		c.702+19571T>G		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+9229T>G		intron	N/A	ENSP00000295101.2	P48549-1
	KCNJ3	ENST00000544049.2	TSL:1	c.702+19571T>G		intron	N/A	ENSP00000438410.1	P48549-2
	KCNJ3	ENST00000651198.1		c.382+9229T>G		intron	N/A	ENSP00000498639.1	A0A494C0M7

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40972 AN: 151618 Hom.: 5740 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.270 AC: 41013 AN: 151736 Hom.: 5748 Cov.: 32 AF XY: 0.272 AC XY: 20137 AN XY: 74140

African (AFR) AF: 0.203 AC: 8403 AN: 41390

American (AMR) AF: 0.275 AC: 4186 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1202 AN: 3466

East Asian (EAS) AF: 0.281 AC: 1442 AN: 5138

South Asian (SAS) AF: 0.299 AC: 1441 AN: 4812

European-Finnish (FIN) AF: 0.308 AC: 3238 AN: 10520

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20036 AN: 67862

Other (OTH) AF: 0.276 AC: 580 AN: 2102

Alfa AF: 0.281 Hom.: 18673

Bravo AF: 0.265

Asia WGS AF: 0.306 AC: 1064 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.89
DANN	Benign	0.84
PhyloP100		-0.38
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: rs3106653; hg19: chr2-155575560;