rs6711727

Variant names:

• chr2-154739926-G-A
• rs6711727
• NM_002239.4:c.919+30107G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-154739926-G-A
• chr2-154739926-G-T

Variant summary

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

The NM_002239.4(KCNJ3):​c.919+30107G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 151,852 control chromosomes in the GnomAD database, including 26,433 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 0.57 (26433 hom., cov: 32)
• Consequence: KCNJ3 NM_002239.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194
• Publications: 3 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002239.4. 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.919+30107G>A		intron	N/A	NP_002230.1
	KCNJ3	NM_001260508.2		c.702+40449G>A		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.919+30107G>A		intron	N/A	ENSP00000295101.2
	KCNJ3	ENST00000544049.2	TSL:1	c.702+40449G>A		intron	N/A	ENSP00000438410.1
	KCNJ3	ENST00000651198.1		c.382+30107G>A		intron	N/A	ENSP00000498639.1

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87101 AN: 151734 Hom.: 26398 Cov.: 32

Gnomad AFR AF: 0.778

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.546

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

GnomAD4 genome AF: 0.574 AC: 87179 AN: 151852 Hom.: 26433 Cov.: 32 AF XY: 0.570 AC XY: 42342 AN XY: 74238

African (AFR) AF: 0.778 AC: 32254 AN: 41454

American (AMR) AF: 0.457 AC: 6967 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1642 AN: 3460

East Asian (EAS) AF: 0.308 AC: 1587 AN: 5160

South Asian (SAS) AF: 0.397 AC: 1911 AN: 4808

European-Finnish (FIN) AF: 0.559 AC: 5906 AN: 10558

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.517 AC: 35079 AN: 67866

Other (OTH) AF: 0.544 AC: 1148 AN: 2110

Alfa AF: 0.538 Hom.: 58904

Bravo AF: 0.578

Asia WGS AF: 0.389 AC: 1353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.17
DANN	Benign	0.56
PhyloP100		-0.19
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: rs6711727; hg19: chr2-155596438;