rs12482611

chr21-38045687-G-A

Variant summary

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

The ENST00000398948.5(DSCR4):n.314+74620C>T variant causes a intron, non coding transcript 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: DSCR4 ENST00000398948.5 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88

Genes affected

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]

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]

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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSCR4	ENST00000398948.5	n.314+74620C>T		intron_variant, non_coding_transcript_variant		5
KCNJ6	ENST00000645093.1	c.-28+74620C>T		intron_variant				P1

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;