rs1399592

Positions:

• chr21-37681559-T-G
• chr21-37681559-T-A
• chr21-37681559-T-C

Variant summary

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

The ENST00000609713.2(KCNJ6):​c.946+32652A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 138,482 control chromosomes in the GnomAD database, including 17,351 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 0.52 (17351 hom., cov: 34)
• Consequence: KCNJ6 ENST00000609713.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.643

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]

KCNJ6-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ6	NM_002240.5	c.946+32652A>C		intron_variant		ENST00000609713.2	NP_002231.1
KCNJ6-AS1	NR_183540.1	n.408-16996T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ6	ENST00000609713.2	c.946+32652A>C		intron_variant		1	NM_002240.5	ENSP00000477437	P1
KCNJ6	ENST00000645093.1	c.946+32652A>C		intron_variant				ENSP00000493772	P1

Frequencies

GnomAD3 genomes AF: 0.523 AC: 72395 AN: 138368 Hom.: 17351 Cov.: 34

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.483

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.572

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.523 AC: 72427 AN: 138482 Hom.: 17351 Cov.: 34 AF XY: 0.524 AC XY: 35394 AN XY: 67600

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.574

Gnomad4 EAS AF: 0.490

Gnomad4 SAS AF: 0.598

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.533

Alfa AF: 0.472 Hom.: 2618

Bravo AF: 0.479

Asia WGS AF: 0.533 AC: 1846 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.2
DANN	Benign	0.82

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: rs1399592; hg19: chr21-39053862;