rs3963114

Variant names:

• chr2-154766240-T-A
• rs3963114
• NM_002239.4:c.919+56421T>A

Your query was ambiguous. Multiple possible variants found:

• chr2-154766240-T-A
• chr2-154766240-T-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+56421T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0288 in 152,328 control chromosomes in the GnomAD database, including 177 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 0.029 (177 hom., cov: 32)
• Consequence: KCNJ3 NM_002239.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.593
• Publications: 1 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.192 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.919+56421T>A		intron	N/A	NP_002230.1
	KCNJ3	NM_001260508.2		c.702+66763T>A		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.919+56421T>A		intron	N/A	ENSP00000295101.2
	KCNJ3	ENST00000544049.2	TSL:1	c.702+66763T>A		intron	N/A	ENSP00000438410.1
	KCNJ3	ENST00000651198.1		c.382+56421T>A		intron	N/A	ENSP00000498639.1

Frequencies

GnomAD3 genomes AF: 0.0288 AC: 4376 AN: 152208 Hom.: 178 Cov.: 32

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.0451

Gnomad AMR AF: 0.0328

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.0722

Gnomad FIN AF: 0.0420

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0206

Gnomad OTH AF: 0.0220

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

GnomAD4 genome AF: 0.0288 AC: 4383 AN: 152328 Hom.: 177 Cov.: 32 AF XY: 0.0316 AC XY: 2357 AN XY: 74480

African (AFR) AF: 0.0118 AC: 490 AN: 41588

American (AMR) AF: 0.0330 AC: 504 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 48 AN: 3468

East Asian (EAS) AF: 0.202 AC: 1050 AN: 5186

South Asian (SAS) AF: 0.0725 AC: 350 AN: 4830

European-Finnish (FIN) AF: 0.0420 AC: 446 AN: 10614

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0207 AC: 1405 AN: 68032

Other (OTH) AF: 0.0217 AC: 46 AN: 2116

Alfa AF: 0.0109 Hom.: 2

Bravo AF: 0.0270

Asia WGS AF: 0.110 AC: 380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	15
DANN	Benign	0.79
PhyloP100		0.59
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: rs3963114; hg19: chr2-155622752;