rs12482570

Positions:

• chr21-37705475-A-G

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ6	NM_002240.5	c.946+8736T>C		intron_variant		ENST00000609713.2	NP_002231.1
KCNJ6-AS1	NR_183540.1	n.548-4839A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ6	ENST00000609713.2	c.946+8736T>C		intron_variant		1	NM_002240.5	ENSP00000477437	P1
KCNJ6-AS1	ENST00000711629.1	n.141-4839A>G		intron_variant, non_coding_transcript_variant
KCNJ6	ENST00000645093.1	c.946+8736T>C		intron_variant				ENSP00000493772	P1

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

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.293

Alfa AF: 0.325 Hom.: 11040

Bravo AF: 0.292

Asia WGS AF: 0.208 AC: 730 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	0.033
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs12482570; hg19: chr21-39077777;