rs10483038

Variant names:

• chr21-37652469-T-C
• rs10483038
• NM_002240.5:c.947-26985A>G

Variant summary

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

The NM_002240.5(KCNJ6):​c.947-26985A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,094 control chromosomes in the GnomAD database, including 5,905 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 0.26 (5905 hom., cov: 32)
• Consequence: KCNJ6 NM_002240.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.845
• 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]

ENSG00000286717 (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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.313 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.947-26985A>G		intron	N/A	NP_002231.1	P48051
	KCNJ6-AS1	NR_183540.1		n.408-46086T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ6	ENST00000609713.2	TSL:1 MANE Select	c.947-26985A>G		intron	N/A	ENSP00000477437.1	P48051
	KCNJ6	ENST00000645093.1		c.947-26985A>G		intron	N/A	ENSP00000493772.1	P48051
	KCNJ6	ENST00000917423.1		c.947-26985A>G		intron	N/A	ENSP00000587482.1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40210 AN: 151978 Hom.: 5900 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.265 AC: 40235 AN: 152094 Hom.: 5905 Cov.: 32 AF XY: 0.268 AC XY: 19894 AN XY: 74352

African (AFR) AF: 0.143 AC: 5945 AN: 41488

American (AMR) AF: 0.289 AC: 4417 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1027 AN: 3472

East Asian (EAS) AF: 0.130 AC: 672 AN: 5178

South Asian (SAS) AF: 0.309 AC: 1487 AN: 4814

European-Finnish (FIN) AF: 0.381 AC: 4024 AN: 10562

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21550 AN: 67978

Other (OTH) AF: 0.271 AC: 572 AN: 2112

Alfa AF: 0.303 Hom.: 3841

Bravo AF: 0.255

Asia WGS AF: 0.179 AC: 629 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	2.1
DANN	Benign	0.47
PhyloP100		-0.84
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10483038;

hg19: chr21-39024771;