rs1040315

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001389.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSCAM	NM_001389.5	MANE Select	c.509-83680T>C		intron	N/A	NP_001380.2
	DSCAM	NM_001271534.3		c.509-83680T>C		intron	N/A	NP_001258463.1
	DSCAM	NR_073202.3		n.1006-83680T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSCAM	ENST00000400454.6	TSL:1 MANE Select	c.509-83680T>C		intron	N/A	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

African (AFR) AF: 0.223 AC: 9229 AN: 41444

American (AMR) AF: 0.349 AC: 5320 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 841 AN: 3470

East Asian (EAS) AF: 0.241 AC: 1239 AN: 5150

South Asian (SAS) AF: 0.182 AC: 878 AN: 4818

European-Finnish (FIN) AF: 0.320 AC: 3381 AN: 10554

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.365 AC: 24801 AN: 67944

Other (OTH) AF: 0.307 AC: 647 AN: 2110

Alfa AF: 0.344 Hom.: 4887

Bravo AF: 0.309

Asia WGS AF: 0.206 AC: 716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Benign	0.85
PhyloP100		2.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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