3-117437408-C-T

Variant names:

• chr3-117437408-C-T
• rs9870146
• ENST00000717962.1:n.536-97621G>A

Variant summary

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

The ENST00000717962.1(LSAMP):​n.536-97621G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 152,054 control chromosomes in the GnomAD database, including 26,693 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 0.54 (26693 hom., cov: 33)
• Consequence: LSAMP ENST00000717962.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233
• Publications: 5 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSAMP	ENST00000717962.1	n.536-97621G>A		intron_variant	Intron 2 of 6

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82448 AN: 151936 Hom.: 26702 Cov.: 33

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.568

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

GnomAD4 genome AF: 0.542 AC: 82437 AN: 152054 Hom.: 26693 Cov.: 33 AF XY: 0.538 AC XY: 40028 AN XY: 74336

African (AFR) AF: 0.182 AC: 7559 AN: 41482

American (AMR) AF: 0.555 AC: 8458 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.672 AC: 2331 AN: 3470

East Asian (EAS) AF: 0.384 AC: 1981 AN: 5156

South Asian (SAS) AF: 0.538 AC: 2599 AN: 4830

European-Finnish (FIN) AF: 0.682 AC: 7217 AN: 10584

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.738 AC: 50143 AN: 67980

Other (OTH) AF: 0.562 AC: 1187 AN: 2112

Alfa AF: 0.592 Hom.: 34335

Bravo AF: 0.519

Asia WGS AF: 0.446 AC: 1555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.9
DANN	Benign	0.79
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9870146; hg19: chr3-117156255;