2-154778066-T-C

Variant names:

• chr2-154778066-T-C
• rs11899272
• NM_002239.4:c.919+68247T>C

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+68247T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,126 control chromosomes in the GnomAD database, including 838 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 0.10 (838 hom., cov: 33)
• Consequence: KCNJ3 NM_002239.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.515
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.18 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+68247T>C		intron	N/A	NP_002230.1
	KCNJ3	NM_001260508.2		c.703-76661T>C		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+68247T>C		intron	N/A	ENSP00000295101.2
	KCNJ3	ENST00000544049.2	TSL:1	c.703-76661T>C		intron	N/A	ENSP00000438410.1
	KCNJ3	ENST00000651198.1		c.382+68247T>C		intron	N/A	ENSP00000498639.1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15294 AN: 152008 Hom.: 837 Cov.: 33

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0738

Gnomad ASJ AF: 0.0824

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.0680

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0847

Gnomad OTH AF: 0.0977

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

GnomAD4 genome AF: 0.101 AC: 15307 AN: 152126 Hom.: 838 Cov.: 33 AF XY: 0.102 AC XY: 7581 AN XY: 74364

African (AFR) AF: 0.129 AC: 5374 AN: 41502

American (AMR) AF: 0.0739 AC: 1130 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0824 AC: 286 AN: 3470

East Asian (EAS) AF: 0.190 AC: 984 AN: 5172

South Asian (SAS) AF: 0.0675 AC: 326 AN: 4832

European-Finnish (FIN) AF: 0.111 AC: 1179 AN: 10578

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0847 AC: 5756 AN: 67970

Other (OTH) AF: 0.0972 AC: 205 AN: 2110

Alfa AF: 0.0988 Hom.: 244

Bravo AF: 0.101

Asia WGS AF: 0.129 AC: 447 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.98
DANN	Benign	0.50
PhyloP100		-0.52
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: rs11899272; hg19: chr2-155634578;