3-115877470-T-C

Variant names:

• chr3-115877470-T-C
• rs9830559
• NM_002338.5:c.515-24853A>G

Variant summary

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

The NM_002338.5(LSAMP):​c.515-24853A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 151,972 control chromosomes in the GnomAD database, including 13,183 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 0.41 (13183 hom., cov: 32)
• Consequence: LSAMP NM_002338.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.413
• Publications: 6 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=-0.47).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LSAMP	NM_002338.5	c.515-24853A>G		intron_variant	Intron 3 of 6	ENST00000490035.7	NP_002329.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSAMP	ENST00000490035.7	c.515-24853A>G		intron_variant	Intron 3 of 6	1	NM_002338.5	ENSP00000419000.1

Frequencies

GnomAD3 genomes AF: 0.415 AC: 62994 AN: 151856 Hom.: 13174 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.418

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

GnomAD4 genome AF: 0.415 AC: 63051 AN: 151972 Hom.: 13183 Cov.: 32 AF XY: 0.419 AC XY: 31149 AN XY: 74276

African (AFR) AF: 0.345 AC: 14294 AN: 41470

American (AMR) AF: 0.467 AC: 7126 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1561 AN: 3470

East Asian (EAS) AF: 0.431 AC: 2218 AN: 5144

South Asian (SAS) AF: 0.522 AC: 2517 AN: 4822

European-Finnish (FIN) AF: 0.460 AC: 4862 AN: 10560

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28945 AN: 67938

Other (OTH) AF: 0.423 AC: 894 AN: 2114

Alfa AF: 0.422 Hom.: 35990

Bravo AF: 0.408

Asia WGS AF: 0.463 AC: 1607 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	15
DANN	Benign	0.74
PhyloP100		0.41
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: rs9830559; hg19: chr3-115596317;