rs12482611

Variant names:

• chr21-38045687-G-A
• rs12482611
• ENST00000645093.1:c.-28+74620C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000645093.1(KCNJ6):​c.-28+74620C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0991 in 152,174 control chromosomes in the GnomAD database, including 1,254 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 0.099 (1254 hom., cov: 33)
• Consequence: KCNJ6 ENST00000645093.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88

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]

DSCR4 (HGNC:3045): (Down syndrome critical region 4) The gene is found in a region of chromosome 21 that has been linked to the pathogenesis of Down syndrome. This gene is transcribed from a bi-directional promoter located in an endogenous retrovirus. [provided by RefSeq, Jan 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ6	ENST00000645093.1	c.-28+74620C>T		intron_variant	Intron 2 of 4			ENSP00000493772.1
DSCR4	ENST00000398948.5	n.314+74620C>T		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.0990 AC: 15057 AN: 152056 Hom.: 1247 Cov.: 33

Gnomad AFR AF: 0.0378

Gnomad AMI AF: 0.00991

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.0800

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.0991 AC: 15075 AN: 152174 Hom.: 1254 Cov.: 33 AF XY: 0.108 AC XY: 8049 AN XY: 74408

Gnomad4 AFR AF: 0.0377

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.0801

Gnomad4 OTH AF: 0.112

Alfa AF: 0.0929 Hom.: 1112

Bravo AF: 0.0960

Asia WGS AF: 0.294 AC: 1024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.5
DANN	Benign	0.24

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12482611; hg19: chr21-39417989;