rs2053672

Positions:

• chr2-154787466-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002239.4(KCNJ3):​c.920-67261C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,058 control chromosomes in the GnomAD database, including 6,570 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 0.26 (6570 hom., cov: 32)
• Consequence: KCNJ3 NM_002239.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ3	NM_002239.4	c.920-67261C>G		intron_variant		ENST00000295101.3	NP_002230.1
KCNJ3	NM_001260508.2	c.703-67261C>G		intron_variant			NP_001247437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ3	ENST00000295101.3	c.920-67261C>G		intron_variant		1	NM_002239.4	ENSP00000295101	P1
KCNJ3	ENST00000544049.2	c.703-67261C>G		intron_variant		1		ENSP00000438410
KCNJ3	ENST00000651198.1	c.383-67261C>G		intron_variant				ENSP00000498639
KCNJ3	ENST00000493505.1	n.263-67261C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39565 AN: 151940 Hom.: 6565 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.260 AC: 39578 AN: 152058 Hom.: 6570 Cov.: 32 AF XY: 0.259 AC XY: 19279 AN XY: 74320

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.233

Alfa AF: 0.232 Hom.: 637

Bravo AF: 0.272

Asia WGS AF: 0.194 AC: 675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2053672; hg19: chr2-155643978;