NM_002240.5:c.946+9552G>A

Variant names:

• chr21-37704659-C-T
• rs1787422
• NM_002240.5:c.946+9552G>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.946+9552G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0476 in 148,612 control chromosomes in the GnomAD database, including 498 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 0.048 (498 hom., cov: 30)
• Consequence: KCNJ6 NM_002240.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720
• Publications: 3 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 (AFR) allele frequency at 95% confidence interval = 0.151 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.946+9552G>A		intron	N/A	NP_002231.1	P48051
	KCNJ6-AS1	NR_183540.1		n.548-5655C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ6	ENST00000609713.2	TSL:1 MANE Select	c.946+9552G>A		intron	N/A	ENSP00000477437.1	P48051
	KCNJ6	ENST00000645093.1		c.946+9552G>A		intron	N/A	ENSP00000493772.1	P48051
	KCNJ6	ENST00000917423.1		c.946+9552G>A		intron	N/A	ENSP00000587482.1

Frequencies

GnomAD3 genomes AF: 0.0474 AC: 7046 AN: 148498 Hom.: 497 Cov.: 30

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0229

Gnomad ASJ AF: 0.000905

Gnomad EAS AF: 0.000198

Gnomad SAS AF: 0.0158

Gnomad FIN AF: 0.000382

Gnomad MID AF: 0.00325

Gnomad NFE AF: 0.00379

Gnomad OTH AF: 0.0406

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

GnomAD4 genome AF: 0.0476 AC: 7071 AN: 148612 Hom.: 498 Cov.: 30 AF XY: 0.0464 AC XY: 3373 AN XY: 72740

African (AFR) AF: 0.154 AC: 6311 AN: 41050

American (AMR) AF: 0.0229 AC: 345 AN: 15086

Ashkenazi Jewish (ASJ) AF: 0.000905 AC: 3 AN: 3314

East Asian (EAS) AF: 0.000198 AC: 1 AN: 5044

South Asian (SAS) AF: 0.0156 AC: 74 AN: 4754

European-Finnish (FIN) AF: 0.000382 AC: 4 AN: 10468

Middle Eastern (MID) AF: 0.00350 AC: 1 AN: 286

European-Non Finnish (NFE) AF: 0.00379 AC: 249 AN: 65712

Other (OTH) AF: 0.0403 AC: 83 AN: 2062

Alfa AF: 0.553 Hom.: 26203

Asia WGS AF: 0.0240 AC: 82 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.54
PhyloP100		-0.072
Mutation Taster		=17/83	disease causing

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: rs1787422; hg19: chr21-39076961; COSMIC: COSV55708914;