rs8130732

Variant names:

• chr21-40151580-A-G
• rs8130732
• NM_001389.5:c.3019-6849T>C

Your query was ambiguous. Multiple possible variants found:

• chr21-40151580-A-G
• chr21-40151580-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.3019-6849T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 152,132 control chromosomes in the GnomAD database, including 42,968 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 0.75 (42968 hom., cov: 33)
• Consequence: DSCAM NM_001389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSCAM	NM_001389.5	c.3019-6849T>C		intron_variant	Intron 16 of 32	ENST00000400454.6	NP_001380.2
DSCAM	NM_001271534.3	c.3019-6849T>C		intron_variant	Intron 16 of 32		NP_001258463.1
DSCAM	XM_017028281.2	c.2311-6849T>C		intron_variant	Intron 13 of 29		XP_016883770.1
DSCAM	NR_073202.3	n.3516-6849T>C		intron_variant	Intron 16 of 32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSCAM	ENST00000400454.6	c.3019-6849T>C		intron_variant	Intron 16 of 32	1	NM_001389.5	ENSP00000383303.1
DSCAM	ENST00000404019.2	c.2275-6849T>C		intron_variant	Intron 12 of 28	1		ENSP00000385342.2
DSCAM	ENST00000617870.4	c.2524-6849T>C		intron_variant	Intron 13 of 29	5		ENSP00000478698.1

Frequencies

GnomAD3 genomes AF: 0.750 AC: 113991 AN: 152014 Hom.: 42924 Cov.: 33

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.909

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.757

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.739

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

GnomAD4 genome AF: 0.750 AC: 114091 AN: 152132 Hom.: 42968 Cov.: 33 AF XY: 0.751 AC XY: 55855 AN XY: 74378

Gnomad4 AFR AF: 0.733

Gnomad4 AMR AF: 0.722

Gnomad4 ASJ AF: 0.757

Gnomad4 EAS AF: 0.724

Gnomad4 SAS AF: 0.831

Gnomad4 FIN AF: 0.768

Gnomad4 NFE AF: 0.758

Gnomad4 OTH AF: 0.742

Alfa AF: 0.759 Hom.: 20124

Bravo AF: 0.747

Asia WGS AF: 0.777 AC: 2700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.3
DANN	Benign	0.50

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: rs8130732; hg19: chr21-41523507;