rs451518

chr21-40107771-C-Tchr21-40107771-C-Achr21-40107771-C-G

Variant summary

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

The NM_001389.5(DSCAM):c.3697-13897G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.891 in 152,126 control chromosomes in the GnomAD database, including 60,585 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 0.89 (60585 hom., cov: 30)
• Consequence: DSCAM NM_001389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.705

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DSCAM	NM_001389.5	c.3697-13897G>A		intron_variant		ENST00000400454.6
DSCAM	NM_001271534.3	c.3697-13897G>A		intron_variant
DSCAM	XM_017028281.2	c.2989-13897G>A		intron_variant
DSCAM	NR_073202.3	n.4194-13897G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSCAM	ENST00000400454.6	c.3697-13897G>A		intron_variant		1	NM_001389.5	P1
DSCAM	ENST00000404019.2	c.2953-13897G>A		intron_variant		1
DSCAM	ENST00000617870.4	c.3202-13897G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.891 AC: 135391 AN: 152008 Hom.: 60532 Cov.: 30

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.993

Gnomad AMR AF: 0.927

Gnomad ASJ AF: 0.980

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.933

Gnomad FIN AF: 0.939

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.914

Gnomad OTH AF: 0.919

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

GnomAD4 genome AF: 0.891 AC: 135502 AN: 152126 Hom.: 60585 Cov.: 30 AF XY: 0.893 AC XY: 66376 AN XY: 74368

Gnomad4 AFR AF: 0.808

Gnomad4 AMR AF: 0.927

Gnomad4 ASJ AF: 0.980

Gnomad4 EAS AF: 0.911

Gnomad4 SAS AF: 0.934

Gnomad4 FIN AF: 0.939

Gnomad4 NFE AF: 0.914

Gnomad4 OTH AF: 0.919

Alfa AF: 0.916 Hom.: 54071

Bravo AF: 0.889

Asia WGS AF: 0.933 AC: 3245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	1.4
Dann	Benign	0.30

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: rs451518; hg19: chr21-41479698;