rs3111034

Variant names:

• chr2-154698578-G-A
• rs3111034
• ENST00000651198.1:c.-43+604G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000651198.1(KCNJ3):​c.-43+604G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 581,718 control chromosomes in the GnomAD database, including 74 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 0.012 (12 hom., cov: 31)
  • Exomes 𝑓: 0.012 (62 hom.)
• Consequence: KCNJ3 ENST00000651198.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• Publications: 2 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]

ENSG00000287900 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0123 (1867/152184) while in subpopulation SAS AF = 0.0261 (126/4824). AF 95% confidence interval is 0.0224. There are 12 homozygotes in GnomAd4. There are 954 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000651198.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ3	NM_002239.4	MANE Select	c.-198G>A		upstream_gene	N/A	NP_002230.1	P48549-1
	KCNJ3	NM_001260509.2		c.-198G>A		upstream_gene	N/A	NP_001247438.1	D2X9V0
	KCNJ3	NM_001260510.2		c.-198G>A		upstream_gene	N/A	NP_001247439.1	D2XBF0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ3	ENST00000651198.1		c.-43+604G>A		intron	N/A	ENSP00000498639.1	A0A494C0M7
	ENSG00000287900	ENST00000803267.1		n.875C>T		non_coding_transcript_exon	Exon 1 of 4
	ENSG00000287900	ENST00000803268.1		n.364C>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.0123 AC: 1867 AN: 152066 Hom.: 12 Cov.: 31

Gnomad AFR AF: 0.00403

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.00962

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.0258

Gnomad SAS AF: 0.0259

Gnomad FIN AF: 0.00839

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.0170

Gnomad OTH AF: 0.0134

GnomAD4 exome AF: 0.0119 AC: 5128 AN: 429534 Hom.: 62 Cov.: 3 AF XY: 0.0122 AC XY: 2741 AN XY: 224316

African (AFR) AF: 0.00230 AC: 28 AN: 12176

American (AMR) AF: 0.00811 AC: 148 AN: 18258

Ashkenazi Jewish (ASJ) AF: 0.00307 AC: 41 AN: 13372

East Asian (EAS) AF: 0.0191 AC: 571 AN: 29898

South Asian (SAS) AF: 0.0210 AC: 843 AN: 40224

European-Finnish (FIN) AF: 0.00642 AC: 210 AN: 32734

Middle Eastern (MID) AF: 0.00738 AC: 14 AN: 1898

European-Non Finnish (NFE) AF: 0.0119 AC: 3055 AN: 256006

Other (OTH) AF: 0.00873 AC: 218 AN: 24968

GnomAD4 genome AF: 0.0123 AC: 1867 AN: 152184 Hom.: 12 Cov.: 31 AF XY: 0.0128 AC XY: 954 AN XY: 74386

African (AFR) AF: 0.00402 AC: 167 AN: 41558

American (AMR) AF: 0.00961 AC: 147 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3468

East Asian (EAS) AF: 0.0259 AC: 132 AN: 5104

South Asian (SAS) AF: 0.0261 AC: 126 AN: 4824

European-Finnish (FIN) AF: 0.00839 AC: 89 AN: 10612

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.0170 AC: 1156 AN: 68002

Other (OTH) AF: 0.0132 AC: 28 AN: 2114

Alfa AF: 0.0162 Hom.: 23

Bravo AF: 0.0119

Asia WGS AF: 0.0180 AC: 64 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.8
DANN	Benign	0.68
PhyloP100		1.2
PromoterAI		-0.042	Neutral
Mutation Taster		=300/0	polymorphism

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: rs3111034; hg19: chr2-155555090;