chr11-117604518-C-T

Variant names:

• chr11-117604518-C-T
• rs680730
• NM_020693.4:c.512-71996G>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.512-71996G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 151,910 control chromosomes in the GnomAD database, including 7,709 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 0.31 (7709 hom., cov: 31)
• Consequence: DSCAML1 NM_020693.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• 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=-0.67).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSCAML1	NM_020693.4	c.512-71996G>A		intron_variant	Intron 3 of 32	ENST00000651296.2	NP_065744.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSCAML1	ENST00000651296.2	c.512-71996G>A		intron_variant	Intron 3 of 32		NM_020693.4	ENSP00000498769.1
DSCAML1	ENST00000321322.6	c.692-71996G>A		intron_variant	Intron 3 of 32	1		ENSP00000315465.6
DSCAML1	ENST00000651172.1	c.692-71996G>A		intron_variant	Intron 3 of 32			ENSP00000498407.1
DSCAML1	ENST00000527706.5	c.103-79509G>A		intron_variant	Intron 2 of 30	5		ENSP00000434335.1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47763 AN: 151792 Hom.: 7704 Cov.: 31

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.315 AC: 47788 AN: 151910 Hom.: 7709 Cov.: 31 AF XY: 0.314 AC XY: 23304 AN XY: 74236

African (AFR) AF: 0.357 AC: 14777 AN: 41446

American (AMR) AF: 0.301 AC: 4591 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1254 AN: 3472

East Asian (EAS) AF: 0.287 AC: 1478 AN: 5148

South Asian (SAS) AF: 0.438 AC: 2096 AN: 4788

European-Finnish (FIN) AF: 0.269 AC: 2838 AN: 10542

Middle Eastern (MID) AF: 0.380 AC: 111 AN: 292

European-Non Finnish (NFE) AF: 0.291 AC: 19755 AN: 67932

Other (OTH) AF: 0.321 AC: 678 AN: 2112

Alfa AF: 0.307 Hom.: 2531

Bravo AF: 0.318

Asia WGS AF: 0.346 AC: 1205 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	4.1
DANN	Benign	0.77
PhyloP100		-1.3
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: rs680730; hg19: chr11-117475233;