ENST00000645093.1:c.-27-124197C>T

Variant names:

• chr21-37964906-G-A
• rs1539902
• ENST00000645093.1:c.-27-124197C>T

Variant summary

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

The ENST00000645093.1(KCNJ6):​c.-27-124197C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 151,948 control chromosomes in the GnomAD database, including 5,984 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 0.28 (5984 hom., cov: 31)
• Consequence: KCNJ6 ENST00000645093.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.412 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.-27-124197C>T		intron_variant	Intron 2 of 4			ENSP00000493772.1
DSCR4	ENST00000398948.5	n.315-11901C>T		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42021 AN: 151830 Hom.: 5979 Cov.: 31

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.277 AC: 42049 AN: 151948 Hom.: 5984 Cov.: 31 AF XY: 0.277 AC XY: 20550 AN XY: 74282

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.427

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.258

Alfa AF: 0.247 Hom.: 6546

Bravo AF: 0.281

Asia WGS AF: 0.373 AC: 1294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1539902; hg19: chr21-39337209;