rs3804024

chr21-40621781-T-Cchr21-40621781-T-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DSCAM	NM_001389.5	c.508+71029A>G		intron_variant		ENST00000400454.6
DSCAM-IT1	NR_046774.2	n.213-381A>G		intron_variant, non_coding_transcript_variant
DSCAM	NM_001271534.3	c.508+71029A>G		intron_variant
DSCAM	NR_073202.3	n.1005+71029A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSCAM	ENST00000400454.6	c.508+71029A>G		intron_variant		1	NM_001389.5	P1
DSCAM-IT1	ENST00000441910.5	n.213-381A>G		intron_variant, non_coding_transcript_variant		5
DSCAM-IT1	ENST00000440363.1	n.213-381A>G		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.0422

Gnomad4 ASJ AF: 0.0312

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.0391

Gnomad4 NFE AF: 0.0794

Gnomad4 OTH AF: 0.0720

Alfa AF: 0.0751 Hom.: 637

Bravo AF: 0.0888

Asia WGS AF: 0.136 AC: 473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.20
Dann	Benign	0.33

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: rs3804024; hg19: chr21-41993707;