NM_002240.5:c.946+32652A>C

Variant names:

• chr21-37681559-T-G
• rs1399592
• NM_002240.5:c.946+32652A>C

Variant summary

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

The NM_002240.5(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 NM_002240.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.643
• Publications: 3 publications found

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:):

KCNJ6-AS1 (HGNC:41352): (KCNJ6 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002240.5. 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
	KCNJ6	NM_002240.5	MANE Select	c.946+32652A>C		intron	N/A	NP_002231.1
	KCNJ6-AS1	NR_183540.1		n.408-16996T>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ6	ENST00000609713.2	TSL:1 MANE Select	c.946+32652A>C		intron	N/A	ENSP00000477437.1
	KCNJ6	ENST00000645093.1		c.946+32652A>C		intron	N/A	ENSP00000493772.1
	KCNJ6-AS1	ENST00000838485.1		n.87-28755T>G		intron	N/A

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

African (AFR) AF: 0.529 AC: 21023 AN: 39714

American (AMR) AF: 0.545 AC: 7528 AN: 13806

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 1774 AN: 3092

East Asian (EAS) AF: 0.490 AC: 2503 AN: 5104

South Asian (SAS) AF: 0.598 AC: 2530 AN: 4234

European-Finnish (FIN) AF: 0.460 AC: 4133 AN: 8976

Middle Eastern (MID) AF: 0.574 AC: 147 AN: 256

European-Non Finnish (NFE) AF: 0.518 AC: 31442 AN: 60706

Other (OTH) AF: 0.533 AC: 1008 AN: 1892

Alfa AF: 0.474 Hom.: 2712

Bravo AF: 0.479

Asia WGS AF: 0.533 AC: 1846 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.2
DANN	Benign	0.82
PhyloP100		-0.64
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: rs1399592; hg19: chr21-39053862;