ENST00000474851.1:c.179-192208G>T

Variant names:

• chr3-116637163-C-A
• rs9847048
• ENST00000474851.1:c.179-192208G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.92).
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSAMP	ENST00000474851.1	c.179-192208G>T		intron_variant	Intron 2 of 4	5		ENSP00000418506.1
LSAMP	ENST00000717962.1	n.687-192208G>T		intron_variant	Intron 4 of 6

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

African (AFR) AF: 0.214 AC: 8887 AN: 41444

American (AMR) AF: 0.224 AC: 3418 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 551 AN: 3470

East Asian (EAS) AF: 0.306 AC: 1583 AN: 5166

South Asian (SAS) AF: 0.198 AC: 955 AN: 4814

European-Finnish (FIN) AF: 0.164 AC: 1733 AN: 10572

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10859 AN: 67990

Other (OTH) AF: 0.163 AC: 344 AN: 2114

Alfa AF: 0.179 Hom.: 1010

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
PhyloP100		0.034
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: rs9847048; hg19: chr3-116356010;