rs1838674

Variant names:

• chr2-154795029-T-C
• rs1838674
• NM_002239.4:c.920-59698T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000295101.3(KCNJ3):​c.920-59698T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 151,898 control chromosomes in the GnomAD database, including 1,991 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 0.15 (1991 hom., cov: 32)
• Consequence: KCNJ3 ENST00000295101.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000295101.3. 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.920-59698T>C		intron	N/A	NP_002230.1
	KCNJ3	NM_001260508.2		c.703-59698T>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.920-59698T>C		intron	N/A	ENSP00000295101.2
	KCNJ3	ENST00000544049.2	TSL:1	c.703-59698T>C		intron	N/A	ENSP00000438410.1
	KCNJ3	ENST00000651198.1		c.383-59698T>C		intron	N/A	ENSP00000498639.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22974 AN: 151778 Hom.: 1993 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.151 AC: 22987 AN: 151898 Hom.: 1991 Cov.: 32 AF XY: 0.153 AC XY: 11339 AN XY: 74254

African (AFR) AF: 0.160 AC: 6647 AN: 41494

American (AMR) AF: 0.168 AC: 2567 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 573 AN: 3462

East Asian (EAS) AF: 0.385 AC: 1982 AN: 5144

South Asian (SAS) AF: 0.217 AC: 1046 AN: 4818

European-Finnish (FIN) AF: 0.111 AC: 1168 AN: 10570

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.124 AC: 8408 AN: 67860

Other (OTH) AF: 0.159 AC: 335 AN: 2106

Alfa AF: 0.133 Hom.: 2370

Bravo AF: 0.157

Asia WGS AF: 0.258 AC: 892 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.58
PhyloP100		-1.5
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: rs1838674; hg19: chr2-155651541;