21-37982733-T-C

Variant names:

• chr21-37982733-T-C
• rs2836079
• ENST00000645093.1:c.-28+137574A>G

Variant summary

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

The ENST00000645093.1(KCNJ6):​c.-28+137574A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 151,982 control chromosomes in the GnomAD database, including 11,297 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 0.38 (11297 hom., cov: 31)
• Consequence: KCNJ6 ENST00000645093.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.498

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.713 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+137574A>G		intron_variant	Intron 2 of 4			ENSP00000493772.1
DSCR4	ENST00000398948.5	n.315-29728A>G		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57206 AN: 151864 Hom.: 11275 Cov.: 31

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.732

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.377 AC: 57272 AN: 151982 Hom.: 11297 Cov.: 31 AF XY: 0.378 AC XY: 28118 AN XY: 74332

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.336

Gnomad4 EAS AF: 0.732

Gnomad4 SAS AF: 0.562

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.389

Alfa AF: 0.373 Hom.: 22142

Bravo AF: 0.385

Asia WGS AF: 0.608 AC: 2106 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.3
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2836079; hg19: chr21-39355035;