3-115854985-T-C

Variant names:

• chr3-115854985-T-C
• rs6763835
• NM_002338.5:c.515-2368A>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.515-2368A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 152,026 control chromosomes in the GnomAD database, including 32,656 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 0.65 (32656 hom., cov: 31)
• Consequence: LSAMP NM_002338.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.645
• Publications: 4 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LSAMP	NM_002338.5	c.515-2368A>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.515-2368A>G		intron_variant	Intron 3 of 6	1	NM_002338.5	ENSP00000419000.1

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99361 AN: 151908 Hom.: 32615 Cov.: 31

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.675

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

GnomAD4 genome AF: 0.654 AC: 99458 AN: 152026 Hom.: 32656 Cov.: 31 AF XY: 0.652 AC XY: 48448 AN XY: 74312

African (AFR) AF: 0.724 AC: 30007 AN: 41470

American (AMR) AF: 0.678 AC: 10364 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2120 AN: 3472

East Asian (EAS) AF: 0.551 AC: 2843 AN: 5162

South Asian (SAS) AF: 0.642 AC: 3091 AN: 4816

European-Finnish (FIN) AF: 0.577 AC: 6095 AN: 10556

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.628 AC: 42705 AN: 67964

Other (OTH) AF: 0.676 AC: 1424 AN: 2106

Alfa AF: 0.638 Hom.: 14886

Bravo AF: 0.662

Asia WGS AF: 0.628 AC: 2186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.1
DANN	Benign	0.70
PhyloP100		-0.65
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: rs6763835; hg19: chr3-115573832;