2-154791854-C-T

Variant names:

• chr2-154791854-C-T
• rs2591157
• NM_002239.4:c.920-62873C>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.920-62873C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 151,892 control chromosomes in the GnomAD database, including 41,509 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 0.73 (41509 hom., cov: 31)
• Consequence: KCNJ3 NM_002239.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.196
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.88 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ3	NM_002239.4	MANE Select	c.920-62873C>T		intron	N/A	NP_002230.1
	KCNJ3	NM_001260508.2		c.703-62873C>T		intron	N/A	NP_001247437.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ3	ENST00000295101.3	TSL:1 MANE Select	c.920-62873C>T		intron	N/A	ENSP00000295101.2
	KCNJ3	ENST00000544049.2	TSL:1	c.703-62873C>T		intron	N/A	ENSP00000438410.1
	KCNJ3	ENST00000651198.1		c.383-62873C>T		intron	N/A	ENSP00000498639.1

Frequencies

GnomAD3 genomes AF: 0.731 AC: 111021 AN: 151774 Hom.: 41484 Cov.: 31

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.722

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

GnomAD4 genome AF: 0.731 AC: 111093 AN: 151892 Hom.: 41509 Cov.: 31 AF XY: 0.725 AC XY: 53804 AN XY: 74214

African (AFR) AF: 0.888 AC: 36824 AN: 41488

American (AMR) AF: 0.622 AC: 9467 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 2715 AN: 3466

East Asian (EAS) AF: 0.482 AC: 2484 AN: 5158

South Asian (SAS) AF: 0.675 AC: 3249 AN: 4810

European-Finnish (FIN) AF: 0.655 AC: 6903 AN: 10534

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.692 AC: 46990 AN: 67900

Other (OTH) AF: 0.719 AC: 1516 AN: 2108

Alfa AF: 0.704 Hom.: 75209

Bravo AF: 0.736

Asia WGS AF: 0.576 AC: 2004 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.8
DANN	Benign	0.80
PhyloP100		-0.20
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: rs2591157; hg19: chr2-155648366;