chr2-154826044-T-C

Position:

• chr2-154826044-T-C

Variant summary

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

The NM_002239.4(KCNJ3):​c.920-28683T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 151,918 control chromosomes in the GnomAD database, including 16,712 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 0.45 (16712 hom., cov: 31)
• Consequence: KCNJ3 NM_002239.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.383

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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ3	NM_002239.4	c.920-28683T>C		intron_variant		ENST00000295101.3	NP_002230.1
KCNJ3	NM_001260508.2	c.703-28683T>C		intron_variant			NP_001247437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ3	ENST00000295101.3	c.920-28683T>C		intron_variant		1	NM_002239.4	ENSP00000295101	P1
KCNJ3	ENST00000544049.2	c.703-28683T>C		intron_variant		1		ENSP00000438410
KCNJ3	ENST00000651198.1	c.383-28683T>C		intron_variant				ENSP00000498639
KCNJ3	ENST00000493505.1	n.263-28683T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68738 AN: 151802 Hom.: 16705 Cov.: 31

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.453 AC: 68783 AN: 151918 Hom.: 16712 Cov.: 31 AF XY: 0.450 AC XY: 33381 AN XY: 74234

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.532

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.546

Gnomad4 OTH AF: 0.472

Alfa AF: 0.523 Hom.: 20466

Bravo AF: 0.442

Asia WGS AF: 0.469 AC: 1628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.94
DANN	Benign	0.53

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: rs1445649; hg19: chr2-155682556;