rs762145

Variant names:

• chr21-37774015-C-T
• rs762145
• NM_002240.5:c.26-58884G>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.26-58884G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 151,968 control chromosomes in the GnomAD database, including 9,546 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 0.35 (9546 hom., cov: 31)
• Consequence: KCNJ6 NM_002240.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• 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: G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000292435 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.366 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.26-58884G>A		intron	N/A	NP_002231.1	P48051

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ6	ENST00000609713.2	TSL:1 MANE Select	c.26-58884G>A		intron	N/A	ENSP00000477437.1	P48051
	KCNJ6	ENST00000645093.1		c.26-58884G>A		intron	N/A	ENSP00000493772.1	P48051
	KCNJ6	ENST00000917423.1		c.26-58884G>A		intron	N/A	ENSP00000587482.1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53430 AN: 151848 Hom.: 9552 Cov.: 31

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.352 AC: 53446 AN: 151968 Hom.: 9546 Cov.: 31 AF XY: 0.347 AC XY: 25766 AN XY: 74284

African (AFR) AF: 0.371 AC: 15358 AN: 41428

American (AMR) AF: 0.348 AC: 5317 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1441 AN: 3468

East Asian (EAS) AF: 0.297 AC: 1529 AN: 5152

South Asian (SAS) AF: 0.258 AC: 1243 AN: 4818

European-Finnish (FIN) AF: 0.284 AC: 2999 AN: 10568

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.358 AC: 24297 AN: 67950

Other (OTH) AF: 0.375 AC: 791 AN: 2108

Alfa AF: 0.341 Hom.: 1534

Bravo AF: 0.355

Asia WGS AF: 0.276 AC: 960 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.59
DANN	Benign	0.29
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: rs762145; hg19: chr21-39146318;