rs1474494

Positions:

• chr21-40147637-A-G
• chr21-40147637-A-T

Variant summary

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

The NM_001389.5(DSCAM):​c.3019-2906T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 152,070 control chromosomes in the GnomAD database, including 19,755 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 0.47 (19755 hom., cov: 33)
• Consequence: DSCAM NM_001389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.789

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSCAM	NM_001389.5	c.3019-2906T>C		intron_variant		ENST00000400454.6	NP_001380.2
DSCAM	NM_001271534.3	c.3019-2906T>C		intron_variant			NP_001258463.1
DSCAM	XM_017028281.2	c.2311-2906T>C		intron_variant			XP_016883770.1
DSCAM	NR_073202.3	n.3516-2906T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSCAM	ENST00000400454.6	c.3019-2906T>C		intron_variant		1	NM_001389.5	ENSP00000383303	P1
DSCAM	ENST00000404019.2	c.2275-2906T>C		intron_variant		1		ENSP00000385342
DSCAM	ENST00000617870.4	c.2524-2906T>C		intron_variant		5		ENSP00000478698

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72136 AN: 151952 Hom.: 19750 Cov.: 33

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.475 AC: 72159 AN: 152070 Hom.: 19755 Cov.: 33 AF XY: 0.482 AC XY: 35822 AN XY: 74328

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.542

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.633

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.596

Gnomad4 OTH AF: 0.482

Alfa AF: 0.565 Hom.: 21658

Bravo AF: 0.454

Asia WGS AF: 0.497 AC: 1722 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.47
DANN	Benign	0.66

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: rs1474494; hg19: chr21-41519564;