21-37862516-C-T

Variant names:

• chr21-37862516-C-T
• rs1016694
• NM_002240.5:c.-27-21807G>A

Variant summary

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

The NM_002240.5(KCNJ6):​c.-27-21807G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 152,098 control chromosomes in the GnomAD database, including 20,223 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 0.51 (20223 hom., cov: 33)
• Consequence: KCNJ6 NM_002240.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 5 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 Gene-Disease associations (from GenCC):

• Keppen-Lubinsky syndrome

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.608 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.-27-21807G>A		intron	N/A	NP_002231.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ6	ENST00000609713.2	TSL:1 MANE Select	c.-27-21807G>A		intron	N/A	ENSP00000477437.1
	KCNJ6	ENST00000645093.1		c.-27-21807G>A		intron	N/A	ENSP00000493772.1
	KCNJ6	ENST00000917423.1		c.-27-21807G>A		intron	N/A	ENSP00000587482.1

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77718 AN: 151982 Hom.: 20186 Cov.: 33

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.541

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

GnomAD4 genome AF: 0.512 AC: 77809 AN: 152098 Hom.: 20223 Cov.: 33 AF XY: 0.517 AC XY: 38424 AN XY: 74342

African (AFR) AF: 0.487 AC: 20188 AN: 41474

American (AMR) AF: 0.619 AC: 9460 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1877 AN: 3470

East Asian (EAS) AF: 0.610 AC: 3158 AN: 5178

South Asian (SAS) AF: 0.582 AC: 2802 AN: 4816

European-Finnish (FIN) AF: 0.498 AC: 5263 AN: 10574

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.490 AC: 33287 AN: 67978

Other (OTH) AF: 0.543 AC: 1148 AN: 2114

Alfa AF: 0.512 Hom.: 25630

Bravo AF: 0.522

Asia WGS AF: 0.612 AC: 2125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.61
DANN	Benign	0.73
PhyloP100		-1.2
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: rs1016694; hg19: chr21-39234818;