rs10483039

Variant names:

• chr21-37678765-G-A
• rs10483039
• NM_002240.5:c.946+35446C>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.946+35446C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0752 in 152,204 control chromosomes in the GnomAD database, including 1,081 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 0.075 (1081 hom., cov: 32)
• Consequence: KCNJ6 NM_002240.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202
• Publications: 0 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 = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ6	NM_002240.5	c.946+35446C>T		intron_variant	Intron 3 of 3	ENST00000609713.2	NP_002231.1
KCNJ6-AS1	NR_183540.1	n.408-19790G>A		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ6	ENST00000609713.2	c.946+35446C>T		intron_variant	Intron 3 of 3	1	NM_002240.5	ENSP00000477437.1
KCNJ6	ENST00000645093.1	c.946+35446C>T		intron_variant	Intron 4 of 4			ENSP00000493772.1
KCNJ6-AS1	ENST00000838485.1	n.87-31549G>A		intron_variant	Intron 1 of 5

Frequencies

GnomAD3 genomes AF: 0.0752 AC: 11430 AN: 152086 Hom.: 1076 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0296

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.0186

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0122

Gnomad OTH AF: 0.0661

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

GnomAD4 genome AF: 0.0752 AC: 11453 AN: 152204 Hom.: 1081 Cov.: 32 AF XY: 0.0750 AC XY: 5584 AN XY: 74434

African (AFR) AF: 0.215 AC: 8927 AN: 41486

American (AMR) AF: 0.0295 AC: 452 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0683 AC: 237 AN: 3472

East Asian (EAS) AF: 0.0187 AC: 97 AN: 5190

South Asian (SAS) AF: 0.149 AC: 720 AN: 4820

European-Finnish (FIN) AF: 0.00160 AC: 17 AN: 10610

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0122 AC: 831 AN: 68004

Other (OTH) AF: 0.0649 AC: 137 AN: 2110

Alfa AF: 0.0245 Hom.: 337

Bravo AF: 0.0792

Asia WGS AF: 0.0990 AC: 343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.4
DANN	Benign	0.74
PhyloP100		0.20
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: rs10483039; hg19: chr21-39051067;