chr21-37645860-T-C

Variant names:

• chr21-37645860-T-C
• rs2835859
• NM_002240.5:c.947-20376A>G

Variant summary

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

The NM_002240.5(KCNJ6):​c.947-20376A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 151,336 control chromosomes in the GnomAD database, including 3,109 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 0.16 (3109 hom., cov: 31)
• Consequence: KCNJ6 NM_002240.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 13 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]

ENSG00000286717 (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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ6	NM_002240.5	c.947-20376A>G		intron_variant	Intron 3 of 3	ENST00000609713.2	NP_002231.1
KCNJ6-AS1	NR_183540.1	n.408-52695T>C		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ6	ENST00000609713.2	c.947-20376A>G		intron_variant	Intron 3 of 3	1	NM_002240.5	ENSP00000477437.1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23845 AN: 151218 Hom.: 3098 Cov.: 31

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0956

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.0917

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.0272

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0741

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.158 AC: 23898 AN: 151336 Hom.: 3109 Cov.: 31 AF XY: 0.154 AC XY: 11399 AN XY: 73868

African (AFR) AF: 0.356 AC: 14688 AN: 41218

American (AMR) AF: 0.0957 AC: 1445 AN: 15104

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 462 AN: 3464

East Asian (EAS) AF: 0.0919 AC: 468 AN: 5090

South Asian (SAS) AF: 0.238 AC: 1134 AN: 4756

European-Finnish (FIN) AF: 0.0272 AC: 286 AN: 10508

Middle Eastern (MID) AF: 0.144 AC: 42 AN: 292

European-Non Finnish (NFE) AF: 0.0741 AC: 5033 AN: 67906

Other (OTH) AF: 0.144 AC: 301 AN: 2086

Alfa AF: 0.0885 Hom.: 1675

Bravo AF: 0.168

Asia WGS AF: 0.189 AC: 654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.11
DANN	Benign	0.30
PhyloP100		-1.5
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: rs2835859; hg19: chr21-39018162;