rs4640244

Positions:

• chr17-21380911-A-G

Variant summary

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

The ENST00000583088.6(KCNJ12):​c.-179+3998A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 151,864 control chromosomes in the GnomAD database, including 8,765 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 0.33 (8765 hom., cov: 32)
• Consequence: KCNJ12 ENST00000583088.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89

Genes affected

KCNJ12 (HGNC:6258): (potassium inwardly rectifying channel subfamily J member 12) This gene encodes an inwardly rectifying K+ channel which may be blocked by divalent cations. This protein is thought to be one of multiple inwardly rectifying channels which contribute to the cardiac inward rectifier current (IK1). The gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ12	NM_021012.5	c.-179+3998A>G		intron_variant		ENST00000583088.6	NP_066292.2
KCNJ12	XM_005256625.6	c.-179+3585A>G		intron_variant			XP_005256682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ12	ENST00000583088.6	c.-179+3998A>G		intron_variant		1	NM_021012.5	ENSP00000463778	P1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49913 AN: 151746 Hom.: 8757 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.329 AC: 49939 AN: 151864 Hom.: 8765 Cov.: 32 AF XY: 0.326 AC XY: 24197 AN XY: 74212

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.349

Alfa AF: 0.385 Hom.: 25861

Bravo AF: 0.320

Asia WGS AF: 0.234 AC: 763 AN: 3252

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0080
DANN	Benign	0.48

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: rs4640244; hg19: chr17-21284223;