rs2918217

Variant names:

• chr3-115827533-C-T
• rs2918217
• NM_002338.5:c.919+14312G>A

Variant summary

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

The NM_002338.5(LSAMP):​c.919+14312G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 151,946 control chromosomes in the GnomAD database, including 5,495 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 0.24 (5495 hom., cov: 31)
• Consequence: LSAMP NM_002338.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111
• Publications: 8 publications found

Genes affected

LSAMP (HGNC:6705): (limbic system associated membrane protein) This gene encodes a member of the immunoglobulin LAMP, OBCAM and neurotrimin (IgLON) family of proteins. The encoded preproprotein is proteolytically processed to generate a neuronal surface glycoprotein. This protein may act as a selective homophilic adhesion molecule during axon guidance and neuronal growth in the developing limbic system. The encoded protein may also function as a tumor suppressor and may play a role in neuropsychiatric disorders. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]

ENSG00000297708 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LSAMP	NM_002338.5	c.919+14312G>A		intron_variant	Intron 6 of 6	ENST00000490035.7	NP_002329.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSAMP	ENST00000490035.7	c.919+14312G>A		intron_variant	Intron 6 of 6	1	NM_002338.5	ENSP00000419000.1

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36010 AN: 151828 Hom.: 5455 Cov.: 31

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.238 AC: 36118 AN: 151946 Hom.: 5495 Cov.: 31 AF XY: 0.239 AC XY: 17780 AN XY: 74262

African (AFR) AF: 0.419 AC: 17338 AN: 41376

American (AMR) AF: 0.337 AC: 5142 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 375 AN: 3472

East Asian (EAS) AF: 0.221 AC: 1140 AN: 5158

South Asian (SAS) AF: 0.133 AC: 640 AN: 4822

European-Finnish (FIN) AF: 0.153 AC: 1616 AN: 10560

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9180 AN: 67974

Other (OTH) AF: 0.232 AC: 489 AN: 2112

Alfa AF: 0.169 Hom.: 6296

Bravo AF: 0.262

Asia WGS AF: 0.217 AC: 754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.2
DANN	Benign	0.71
PhyloP100		0.11
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: rs2918217; hg19: chr3-115546380;