ENST00000717962.1:n.536-104150G>A

Variant names:

• chr3-117443937-C-T
• rs4075039
• ENST00000717962.1:n.536-104150G>A

Variant summary

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

The ENST00000717962.1(LSAMP):​n.536-104150G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,088 control chromosomes in the GnomAD database, including 3,543 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 0.20 (3543 hom., cov: 33)
• Consequence: LSAMP ENST00000717962.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.525
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.511 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.536-104150G>A		intron_variant	Intron 2 of 6

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29863 AN: 151970 Hom.: 3536 Cov.: 33

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.197 AC: 29893 AN: 152088 Hom.: 3543 Cov.: 33 AF XY: 0.208 AC XY: 15465 AN XY: 74336

African (AFR) AF: 0.121 AC: 5018 AN: 41508

American (AMR) AF: 0.295 AC: 4500 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 768 AN: 3468

East Asian (EAS) AF: 0.527 AC: 2724 AN: 5164

South Asian (SAS) AF: 0.253 AC: 1222 AN: 4824

European-Finnish (FIN) AF: 0.301 AC: 3176 AN: 10546

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11775 AN: 67982

Other (OTH) AF: 0.209 AC: 442 AN: 2112

Alfa AF: 0.181 Hom.: 8905

Bravo AF: 0.193

Asia WGS AF: 0.374 AC: 1296 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.64
DANN	Benign	0.49
PhyloP100		-0.53
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: rs4075039; hg19: chr3-117162784;