rs1040315

Variant names:

• chr21-40452925-A-G
• rs1040315
• NM_001389.5:c.509-83680T>C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001389.5(DSCAM):​c.509-83680T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 151,950 control chromosomes in the GnomAD database, including 7,573 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 0.31 (7573 hom., cov: 30)
• Consequence: DSCAM NM_001389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.73

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSCAM	NM_001389.5	c.509-83680T>C		intron_variant	Intron 3 of 32	ENST00000400454.6	NP_001380.2
DSCAM	NM_001271534.3	c.509-83680T>C		intron_variant	Intron 3 of 32		NP_001258463.1
DSCAM	NR_073202.3	n.1006-83680T>C		intron_variant	Intron 3 of 32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSCAM	ENST00000400454.6	c.509-83680T>C		intron_variant	Intron 3 of 32	1	NM_001389.5	ENSP00000383303.1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46833 AN: 151830 Hom.: 7575 Cov.: 30

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.308 AC: 46835 AN: 151950 Hom.: 7573 Cov.: 30 AF XY: 0.304 AC XY: 22587 AN XY: 74266

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.307

Alfa AF: 0.344 Hom.: 4380

Bravo AF: 0.309

Asia WGS AF: 0.206 AC: 716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Benign	0.85

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: rs1040315; hg19: chr21-41824852; COSMIC: COSV68652452;