rs9847048

Positions:

• chr3-116637163-C-A

Variant summary

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

The ENST00000474851.1(LSAMP):​c.179-192208G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,052 control chromosomes in the GnomAD database, including 2,836 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 0.19 (2836 hom., cov: 32)
• Consequence: LSAMP ENST00000474851.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LSAMP	ENST00000474851.1	c.179-192208G>T		intron_variant		5		ENSP00000418506

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28470 AN: 151934 Hom.: 2829 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.187 AC: 28506 AN: 152052 Hom.: 2836 Cov.: 32 AF XY: 0.189 AC XY: 14064 AN XY: 74318

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.163

Alfa AF: 0.172 Hom.: 506

Bravo AF: 0.195

Asia WGS AF: 0.219 AC: 758 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9847048; hg19: chr3-116356010;