NM_002240.5:c.946+8736T>C

Variant names:

• chr21-37705475-A-G
• rs12482570
• NM_002240.5:c.946+8736T>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+8736T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,144 control chromosomes in the GnomAD database, including 7,065 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 0.30 (7065 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.323 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.946+8736T>C		intron	N/A	NP_002231.1
	KCNJ6-AS1	NR_183540.1		n.548-4839A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ6	ENST00000609713.2	TSL:1 MANE Select	c.946+8736T>C		intron	N/A	ENSP00000477437.1
	KCNJ6	ENST00000645093.1		c.946+8736T>C		intron	N/A	ENSP00000493772.1
	KCNJ6-AS1	ENST00000711629.1		n.141-4839A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45303 AN: 152024 Hom.: 7057 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.298 AC: 45339 AN: 152144 Hom.: 7065 Cov.: 32 AF XY: 0.301 AC XY: 22357 AN XY: 74392

African (AFR) AF: 0.234 AC: 9709 AN: 41504

American (AMR) AF: 0.301 AC: 4609 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1146 AN: 3472

East Asian (EAS) AF: 0.130 AC: 673 AN: 5182

South Asian (SAS) AF: 0.330 AC: 1593 AN: 4822

European-Finnish (FIN) AF: 0.396 AC: 4190 AN: 10584

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.327 AC: 22231 AN: 67966

Other (OTH) AF: 0.293 AC: 619 AN: 2114

Alfa AF: 0.323 Hom.: 13771

Bravo AF: 0.292

Asia WGS AF: 0.208 AC: 730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.033
DANN	Benign	0.51
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: rs12482570; hg19: chr21-39077777;