chr3-117453486-C-A

Variant names:

• chr3-117453486-C-A
• rs10511371
• ENST00000717962.1:n.536-113699G>T

Variant summary

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

The ENST00000717962.1(LSAMP):​n.536-113699G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0982 in 152,126 control chromosomes in the GnomAD database, including 1,638 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 0.098 (1638 hom., cov: 32)
• Consequence: LSAMP ENST00000717962.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344
• Publications: 0 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.264 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.536-113699G>T		intron_variant	Intron 2 of 6

Frequencies

GnomAD3 genomes AF: 0.0981 AC: 14912 AN: 152008 Hom.: 1635 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0737

Gnomad ASJ AF: 0.0283

Gnomad EAS AF: 0.0623

Gnomad SAS AF: 0.0947

Gnomad FIN AF: 0.0156

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0207

Gnomad OTH AF: 0.0900

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

GnomAD4 genome AF: 0.0982 AC: 14943 AN: 152126 Hom.: 1638 Cov.: 32 AF XY: 0.0977 AC XY: 7267 AN XY: 74388

African (AFR) AF: 0.269 AC: 11138 AN: 41464

American (AMR) AF: 0.0739 AC: 1128 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0283 AC: 98 AN: 3468

East Asian (EAS) AF: 0.0622 AC: 322 AN: 5176

South Asian (SAS) AF: 0.0948 AC: 457 AN: 4820

European-Finnish (FIN) AF: 0.0156 AC: 165 AN: 10608

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0207 AC: 1407 AN: 68008

Other (OTH) AF: 0.0896 AC: 189 AN: 2110

Alfa AF: 0.0467 Hom.: 594

Bravo AF: 0.109

Asia WGS AF: 0.0900 AC: 311 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.3
DANN	Benign	0.78
PhyloP100		-0.34
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: rs10511371; hg19: chr3-117172333;