rs12152040

Positions:

• chr21-40697142-T-C

Variant summary

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

The NM_001389.5(DSCAM):​c.362-4186A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,132 control chromosomes in the GnomAD database, including 1,454 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 0.13 (1454 hom., cov: 32)
• Consequence: DSCAM NM_001389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385

Genes affected

DSCAM (HGNC:3039): (DS cell adhesion molecule) This gene is a member of the immunoglobulin superfamily of cell adhesion molecules (Ig-CAMs), and is involved in human central and peripheral nervous system development. This gene is a candidate for Down syndrome and congenital heart disease (DSCHD). A gene encoding a similar Ig-CAM protein is located on chromosome 11. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2012]

DSCAM (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSCAM	NM_001389.5	c.362-4186A>G		intron_variant		ENST00000400454.6	NP_001380.2
DSCAM	NM_001271534.3	c.362-4186A>G		intron_variant			NP_001258463.1
DSCAM	NR_073202.3	n.859-4186A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSCAM	ENST00000400454.6	c.362-4186A>G		intron_variant		1	NM_001389.5	ENSP00000383303.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20377 AN: 152014 Hom.: 1450 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.0670

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.0710

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.134 AC: 20405 AN: 152132 Hom.: 1454 Cov.: 32 AF XY: 0.135 AC XY: 10054 AN XY: 74366

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.0713

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.149

Alfa AF: 0.126 Hom.: 1757

Bravo AF: 0.139

Asia WGS AF: 0.116 AC: 403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.5
DANN	Benign	0.65

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: rs12152040; hg19: chr21-42069068;