3-116726477-T-G

Variant names:

• chr3-116726477-T-G
• rs1432364
• ENST00000474851.1:c.179-281522A>C

Variant summary

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

The ENST00000474851.1(LSAMP):​c.179-281522A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 151,714 control chromosomes in the GnomAD database, including 21,224 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 0.48 (21224 hom., cov: 31)
• Consequence: LSAMP ENST00000474851.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.470
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000474851.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSAMP	ENST00000474851.1	TSL:5	c.179-281522A>C		intron	N/A	ENSP00000418506.1
	LSAMP	ENST00000717962.1		n.687-281522A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73526 AN: 151596 Hom.: 21225 Cov.: 31

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.485 AC: 73527 AN: 151714 Hom.: 21224 Cov.: 31 AF XY: 0.484 AC XY: 35874 AN XY: 74112

African (AFR) AF: 0.153 AC: 6359 AN: 41452

American (AMR) AF: 0.526 AC: 7999 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2082 AN: 3462

East Asian (EAS) AF: 0.685 AC: 3518 AN: 5134

South Asian (SAS) AF: 0.481 AC: 2321 AN: 4824

European-Finnish (FIN) AF: 0.570 AC: 5999 AN: 10526

Middle Eastern (MID) AF: 0.517 AC: 151 AN: 292

European-Non Finnish (NFE) AF: 0.640 AC: 43391 AN: 67802

Other (OTH) AF: 0.501 AC: 1054 AN: 2104

Alfa AF: 0.520 Hom.: 6571

Bravo AF: 0.471

Asia WGS AF: 0.550 AC: 1913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.6
DANN	Benign	0.64
PhyloP100		0.47
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: rs1432364; hg19: chr3-116445324;