11-117518217-C-T

Variant names:

• chr11-117518217-C-T
• rs11216435
• NM_020693.4:c.1510+249G>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.1510+249G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 151,446 control chromosomes in the GnomAD database, including 5,661 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 0.26 (5661 hom., cov: 31)
• Consequence: DSCAML1 NM_020693.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.472
• Publications: 8 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSCAML1	NM_020693.4	c.1510+249G>A		intron_variant	Intron 7 of 32	ENST00000651296.2	NP_065744.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSCAML1	ENST00000651296.2	c.1510+249G>A		intron_variant	Intron 7 of 32		NM_020693.4	ENSP00000498769.1
DSCAML1	ENST00000321322.6	c.1690+249G>A		intron_variant	Intron 7 of 32	1		ENSP00000315465.6
DSCAML1	ENST00000651172.1	c.1690+249G>A		intron_variant	Intron 7 of 32			ENSP00000498407.1
DSCAML1	ENST00000527706.5	c.880+249G>A		intron_variant	Intron 5 of 30	5		ENSP00000434335.1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 39876 AN: 151326 Hom.: 5658 Cov.: 31

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.263 AC: 39902 AN: 151446 Hom.: 5661 Cov.: 31 AF XY: 0.272 AC XY: 20144 AN XY: 73934

African (AFR) AF: 0.327 AC: 13469 AN: 41204

American (AMR) AF: 0.255 AC: 3877 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 887 AN: 3464

East Asian (EAS) AF: 0.305 AC: 1565 AN: 5132

South Asian (SAS) AF: 0.416 AC: 1987 AN: 4776

European-Finnish (FIN) AF: 0.323 AC: 3377 AN: 10470

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14022 AN: 67886

Other (OTH) AF: 0.216 AC: 453 AN: 2094

Alfa AF: 0.228 Hom.: 5440

Bravo AF: 0.256

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.50
PhyloP100		-0.47
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: rs11216435; hg19: chr11-117388932;