chr21-37632199-G-A

Variant names:

• chr21-37632199-G-A
• rs2154553
• NM_002240.5:c.947-6715C>T

Variant summary

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

The NM_002240.5(KCNJ6):​c.947-6715C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 149,722 control chromosomes in the GnomAD database, including 37,803 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 0.71 (37803 hom., cov: 28)
• Consequence: KCNJ6 NM_002240.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ6	NM_002240.5	c.947-6715C>T		intron_variant	Intron 3 of 3	ENST00000609713.2	NP_002231.1
KCNJ6-AS1	NR_183540.1	n.408-66356G>A		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ6	ENST00000609713.2	c.947-6715C>T		intron_variant	Intron 3 of 3	1	NM_002240.5	ENSP00000477437.1
KCNJ6	ENST00000645093.1	c.947-6715C>T		intron_variant	Intron 4 of 4			ENSP00000493772.1
ENSG00000286717	ENST00000667151.1	n.161-14348G>A		intron_variant	Intron 1 of 2
ENSG00000286717	ENST00000838658.1	n.235-26995G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.708 AC: 105885 AN: 149606 Hom.: 37781 Cov.: 28

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.704

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

GnomAD4 genome AF: 0.708 AC: 105956 AN: 149722 Hom.: 37803 Cov.: 28 AF XY: 0.706 AC XY: 51552 AN XY: 73012

African (AFR) AF: 0.731 AC: 30055 AN: 41128

American (AMR) AF: 0.763 AC: 11374 AN: 14904

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2372 AN: 3446

East Asian (EAS) AF: 0.825 AC: 4121 AN: 4994

South Asian (SAS) AF: 0.672 AC: 3191 AN: 4752

European-Finnish (FIN) AF: 0.633 AC: 6416 AN: 10140

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.690 AC: 46313 AN: 67096

Other (OTH) AF: 0.703 AC: 1454 AN: 2068

Alfa AF: 0.697 Hom.: 45973

Bravo AF: 0.717

Asia WGS AF: 0.772 AC: 2680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.71
PhyloP100		-0.092
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: rs2154553; hg19: chr21-39004501;