ENST00000474851.1:c.178+92989G>T

Variant names:

• chr3-116916241-C-A
• rs4258973
• ENST00000474851.1:c.178+92989G>T

Variant summary

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

The ENST00000474851.1(LSAMP):​c.178+92989G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 151,972 control chromosomes in the GnomAD database, including 8,546 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 0.32 (8546 hom., cov: 32)
• Consequence: LSAMP ENST00000474851.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSAMP	ENST00000474851.1	TSL:5	c.178+92989G>T		intron	N/A	ENSP00000418506.1
	LSAMP	ENST00000717962.1		n.686+93041G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48808 AN: 151854 Hom.: 8536 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.321 AC: 48857 AN: 151972 Hom.: 8546 Cov.: 32 AF XY: 0.320 AC XY: 23737 AN XY: 74282

African (AFR) AF: 0.473 AC: 19600 AN: 41446

American (AMR) AF: 0.272 AC: 4154 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1085 AN: 3470

East Asian (EAS) AF: 0.202 AC: 1046 AN: 5168

South Asian (SAS) AF: 0.376 AC: 1810 AN: 4818

European-Finnish (FIN) AF: 0.236 AC: 2483 AN: 10542

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17711 AN: 67952

Other (OTH) AF: 0.301 AC: 635 AN: 2110

Alfa AF: 0.160 Hom.: 328

Bravo AF: 0.330

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	9.8
DANN	Benign	0.70
PhyloP100		1.2
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: rs4258973; hg19: chr3-116635088;