NM_020693.4:c.46+7474G>C

Variant names:

• chr11-117789560-C-G
• rs948100
• NM_020693.4:c.46+7474G>C

Variant summary

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

The NM_020693.4(DSCAML1):​c.46+7474G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,182 control chromosomes in the GnomAD database, including 1,158 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 0.12 (1158 hom., cov: 32)
• Consequence: DSCAML1 NM_020693.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.551
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.146 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.46+7474G>C		intron	N/A	NP_065744.3
	DSCAML1	NM_001367904.1		c.46+7474G>C		intron	N/A	NP_001354833.1
	DSCAML1	NM_001367905.1		c.-362-8750G>C		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.46+7474G>C		intron	N/A	ENSP00000498769.1	Q8TD84-1
	DSCAML1	ENST00000321322.6	TSL:1	c.226+7474G>C		intron	N/A	ENSP00000315465.6	A0A384DVL8
	DSCAML1	ENST00000651172.1		c.226+7474G>C		intron	N/A	ENSP00000498407.1	A0A384DVL8

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18043 AN: 152066 Hom.: 1152 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.0220

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0932

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.119 AC: 18067 AN: 152182 Hom.: 1158 Cov.: 32 AF XY: 0.119 AC XY: 8879 AN XY: 74414

African (AFR) AF: 0.146 AC: 6068 AN: 41500

American (AMR) AF: 0.109 AC: 1664 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 417 AN: 3472

East Asian (EAS) AF: 0.154 AC: 799 AN: 5172

South Asian (SAS) AF: 0.130 AC: 626 AN: 4830

European-Finnish (FIN) AF: 0.0932 AC: 987 AN: 10594

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7178 AN: 67998

Other (OTH) AF: 0.124 AC: 263 AN: 2114

Alfa AF: 0.0285 Hom.: 30

Bravo AF: 0.122

Asia WGS AF: 0.137 AC: 476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.49
PhyloP100		-0.55
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: rs948100; hg19: chr11-117660275;