rs498889

Variant names:

• chr11-117588947-T-C
• rs498889
• NM_020693.4:c.512-56425A>G

Variant summary

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

The NM_020693.4(DSCAML1):​c.512-56425A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,068 control chromosomes in the GnomAD database, including 3,817 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 0.21 (3817 hom., cov: 32)
• Consequence: DSCAML1 NM_020693.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• Publications: 1 publications found

Genes affected

DSCAML1 (HGNC:14656): (DS cell adhesion molecule like 1) The protein encoded by this gene is a member of the Ig superfamily of cell adhesion molecules and is involved in neuronal differentiation. The encoded membrane-bound protein localizes to the cell surface, where it forms aggregates that repel neuronal processes of the same cell type. [provided by RefSeq, Sep 2016]

DSCAML1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• motor neuron disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• retinal disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• retinitis pigmentosa

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020693.4. 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
	DSCAML1	NM_020693.4	MANE Select	c.512-56425A>G		intron	N/A	NP_065744.3
	DSCAML1	NM_001367904.1		c.512-56425A>G		intron	N/A	NP_001354833.1
	DSCAML1	NM_001367905.1		c.104-56425A>G		intron	N/A	NP_001354834.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSCAML1	ENST00000651296.2	MANE Select	c.512-56425A>G		intron	N/A	ENSP00000498769.1
	DSCAML1	ENST00000321322.6	TSL:1	c.692-56425A>G		intron	N/A	ENSP00000315465.6
	DSCAML1	ENST00000651172.1		c.692-56425A>G		intron	N/A	ENSP00000498407.1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32406 AN: 151950 Hom.: 3819 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.213 AC: 32418 AN: 152068 Hom.: 3817 Cov.: 32 AF XY: 0.218 AC XY: 16205 AN XY: 74342

African (AFR) AF: 0.132 AC: 5474 AN: 41480

American (AMR) AF: 0.261 AC: 3995 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1039 AN: 3470

East Asian (EAS) AF: 0.215 AC: 1114 AN: 5170

South Asian (SAS) AF: 0.456 AC: 2189 AN: 4800

European-Finnish (FIN) AF: 0.214 AC: 2269 AN: 10590

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15480 AN: 67964

Other (OTH) AF: 0.229 AC: 483 AN: 2110

Alfa AF: 0.223 Hom.: 523

Bravo AF: 0.209

Asia WGS AF: 0.301 AC: 1044 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	17
DANN	Benign	0.64
PhyloP100		1.4
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: rs498889; hg19: chr11-117459662;