rs13030348

Positions:

• chr2-154838542-T-C
• chr2-154838542-T-G

Variant summary

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

The NM_002239.4(KCNJ3):​c.920-16185T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,084 control chromosomes in the GnomAD database, including 6,727 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 0.28 (6727 hom., cov: 32)
• Consequence: KCNJ3 NM_002239.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNJ3	NM_002239.4	c.920-16185T>C		intron_variant		ENST00000295101.3
KCNJ3	NM_001260508.2	c.703-16185T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ3	ENST00000295101.3	c.920-16185T>C		intron_variant		1	NM_002239.4	P1
KCNJ3	ENST00000544049.2	c.703-16185T>C		intron_variant		1
KCNJ3	ENST00000651198.1	c.383-16185T>C		intron_variant
KCNJ3	ENST00000493505.1	n.263-16185T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42048 AN: 151966 Hom.: 6727 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.277 AC: 42061 AN: 152084 Hom.: 6727 Cov.: 32 AF XY: 0.274 AC XY: 20395 AN XY: 74368

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.289

Alfa AF: 0.302 Hom.: 1255

Bravo AF: 0.261

Asia WGS AF: 0.200 AC: 698 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.9
DANN	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs13030348; hg19: chr2-155695054;