11-117724796-C-T

Variant names:

• chr11-117724796-C-T
• rs11216517
• NM_020693.4:c.511+51995G>A

Variant summary

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

The NM_020693.4(DSCAML1):​c.511+51995G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,234 control chromosomes in the GnomAD database, including 2,145 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 0.15 (2145 hom., cov: 33)
• Consequence: DSCAML1 NM_020693.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.28 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSCAML1	NM_020693.4	MANE Select	c.511+51995G>A		intron	N/A	NP_065744.3
	DSCAML1	NM_001367904.1		c.511+51995G>A		intron	N/A	NP_001354833.1
	DSCAML1	NM_001367905.1		c.103+51995G>A		intron	N/A	NP_001354834.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSCAML1	ENST00000651296.2	MANE Select	c.511+51995G>A		intron	N/A	ENSP00000498769.1
	DSCAML1	ENST00000321322.6	TSL:1	c.691+51995G>A		intron	N/A	ENSP00000315465.6
	DSCAML1	ENST00000651172.1		c.691+51995G>A		intron	N/A	ENSP00000498407.1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22572 AN: 152116 Hom.: 2148 Cov.: 33

Gnomad AFR AF: 0.0366

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.148 AC: 22559 AN: 152234 Hom.: 2145 Cov.: 33 AF XY: 0.154 AC XY: 11464 AN XY: 74408

African (AFR) AF: 0.0365 AC: 1516 AN: 41574

American (AMR) AF: 0.194 AC: 2972 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 520 AN: 3472

East Asian (EAS) AF: 0.293 AC: 1511 AN: 5162

South Asian (SAS) AF: 0.202 AC: 976 AN: 4822

European-Finnish (FIN) AF: 0.261 AC: 2769 AN: 10592

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11873 AN: 68000

Other (OTH) AF: 0.155 AC: 327 AN: 2114

Alfa AF: 0.163 Hom.: 7330

Bravo AF: 0.141

Asia WGS AF: 0.216 AC: 748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.071
DANN	Benign	0.18
PhyloP100		-1.1
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: rs11216517; hg19: chr11-117595511;