21-37693327-A-G

Variant names:

• chr21-37693327-A-G
• rs858008
• NM_002240.5:c.946+20884T>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+20884T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 152,042 control chromosomes in the GnomAD database, including 25,324 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 (25324 hom., cov: 32)
• Consequence: KCNJ6 NM_002240.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 6 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ6	NM_002240.5	MANE Select	c.946+20884T>C		intron	N/A	NP_002231.1	P48051
	KCNJ6-AS1	NR_183540.1		n.408-5228A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ6	ENST00000609713.2	TSL:1 MANE Select	c.946+20884T>C		intron	N/A	ENSP00000477437.1	P48051
	KCNJ6	ENST00000645093.1		c.946+20884T>C		intron	N/A	ENSP00000493772.1	P48051
	KCNJ6	ENST00000917423.1		c.946+20884T>C		intron	N/A	ENSP00000587482.1

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86826 AN: 151924 Hom.: 25276 Cov.: 32

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.572 AC: 86936 AN: 152042 Hom.: 25324 Cov.: 32 AF XY: 0.571 AC XY: 42483 AN XY: 74358

African (AFR) AF: 0.682 AC: 28262 AN: 41470

American (AMR) AF: 0.541 AC: 8259 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1961 AN: 3472

East Asian (EAS) AF: 0.576 AC: 2976 AN: 5166

South Asian (SAS) AF: 0.633 AC: 3053 AN: 4824

European-Finnish (FIN) AF: 0.530 AC: 5591 AN: 10554

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34855 AN: 67958

Other (OTH) AF: 0.564 AC: 1193 AN: 2114

Alfa AF: 0.533 Hom.: 65885

Bravo AF: 0.580

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.6
DANN	Benign	0.18
PhyloP100		-1.1
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: rs858008; hg19: chr21-39065630;