rs8128418

Positions:

• chr21-37816429-C-T
• chr21-37816429-C-A

Variant summary

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

The NM_002240.5(KCNJ6):​c.25+24229G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0756 in 152,244 control chromosomes in the GnomAD database, including 493 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 0.076 (493 hom., cov: 33)
• Consequence: KCNJ6 NM_002240.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.59

Genes affected

KCNJ6 (HGNC:6267): (potassium inwardly rectifying channel subfamily J member 6) This gene encodes a member of the G protein-coupled inwardly-rectifying potassium channel family of inward rectifier potassium channels. This type of potassium channel allows a greater flow of potassium into the cell than out of it. These proteins modulate many physiological processes, including heart rate in cardiac cells and circuit activity in neuronal cells, through G-protein coupled receptor stimulation. Mutations in this gene are associated with Keppen-Lubinsky Syndrome, a rare condition characterized by severe developmental delay, facial dysmorphism, and intellectual disability. [provided by RefSeq, Apr 2015]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNJ6	NM_002240.5	c.25+24229G>A		intron_variant		ENST00000609713.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ6	ENST00000609713.2	c.25+24229G>A		intron_variant		1	NM_002240.5	P1
	ENST00000692486.2	n.176+179C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0756 AC: 11504 AN: 152126 Hom.: 493 Cov.: 33

Gnomad AFR AF: 0.0664

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0558

Gnomad ASJ AF: 0.0936

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0265

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0895

Gnomad OTH AF: 0.0808

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

GnomAD4 genome AF: 0.0756 AC: 11513 AN: 152244 Hom.: 493 Cov.: 33 AF XY: 0.0751 AC XY: 5589 AN XY: 74424

Gnomad4 AFR AF: 0.0664

Gnomad4 AMR AF: 0.0557

Gnomad4 ASJ AF: 0.0936

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0270

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.0895

Gnomad4 OTH AF: 0.0799

Alfa AF: 0.0815 Hom.: 763

Bravo AF: 0.0725

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0010
DANN	Benign	0.55

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: rs8128418; hg19: chr21-39188732;