rs1543175

Variant names:

• chr3-116668062-G-A
• rs1543175
• ENST00000474851.1:c.179-223107C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000474851.1(LSAMP):​c.179-223107C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 152,054 control chromosomes in the GnomAD database, including 17,785 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 0.45 (17785 hom., cov: 33)
• Consequence: LSAMP ENST00000474851.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.599 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	ENST00000474851.1	c.179-223107C>T		intron_variant	Intron 2 of 4	5		ENSP00000418506.1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68111 AN: 151936 Hom.: 17789 Cov.: 33

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.448 AC: 68110 AN: 152054 Hom.: 17785 Cov.: 33 AF XY: 0.444 AC XY: 33037 AN XY: 74330

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.396

Gnomad4 ASJ AF: 0.558

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.604

Gnomad4 OTH AF: 0.431

Alfa AF: 0.573 Hom.: 44773

Bravo AF: 0.421

Asia WGS AF: 0.322 AC: 1120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.1
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1543175; hg19: chr3-116386909;