chr21-40621781-T-C

Variant names:

• chr21-40621781-T-C
• rs3804024
• NM_001389.5:c.508+71029A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001389.5(DSCAM):​c.508+71029A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0899 in 151,284 control chromosomes in the GnomAD database, including 713 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 0.090 (713 hom., cov: 29)
• Consequence: DSCAM NM_001389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79
• Publications: 8 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-IT1 (HGNC:41327): (DSCAM intronic transcript 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.146 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSCAM	NM_001389.5	MANE Select	c.508+71029A>G		intron	N/A	NP_001380.2
	DSCAM	NM_001271534.3		c.508+71029A>G		intron	N/A	NP_001258463.1
	DSCAM-IT1	NR_046774.2		n.213-381A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSCAM	ENST00000400454.6	TSL:1 MANE Select	c.508+71029A>G		intron	N/A	ENSP00000383303.1
	DSCAM-IT1	ENST00000440363.1	TSL:3	n.213-381A>G		intron	N/A
	DSCAM-IT1	ENST00000441910.5	TSL:5	n.213-381A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0899 AC: 13597 AN: 151166 Hom.: 713 Cov.: 29

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0905

Gnomad AMR AF: 0.0423

Gnomad ASJ AF: 0.0312

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.0391

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.0794

Gnomad OTH AF: 0.0728

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

GnomAD4 genome AF: 0.0899 AC: 13598 AN: 151284 Hom.: 713 Cov.: 29 AF XY: 0.0884 AC XY: 6534 AN XY: 73892

African (AFR) AF: 0.131 AC: 5397 AN: 41194

American (AMR) AF: 0.0422 AC: 642 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.0312 AC: 108 AN: 3462

East Asian (EAS) AF: 0.132 AC: 673 AN: 5100

South Asian (SAS) AF: 0.155 AC: 742 AN: 4774

European-Finnish (FIN) AF: 0.0391 AC: 406 AN: 10394

Middle Eastern (MID) AF: 0.0274 AC: 8 AN: 292

European-Non Finnish (NFE) AF: 0.0794 AC: 5389 AN: 67854

Other (OTH) AF: 0.0720 AC: 151 AN: 2096

Alfa AF: 0.0793 Hom.: 1042

Bravo AF: 0.0888

Asia WGS AF: 0.136 AC: 473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.20
DANN	Benign	0.33
PhyloP100		-2.8
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: rs3804024; hg19: chr21-41993707;