3-116839488-A-G

Position:

• chr3-116839488-A-G

Variant summary

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

The ENST00000474851.1(LSAMP):​c.178+169742T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 151,926 control chromosomes in the GnomAD database, including 3,916 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 0.23 (3916 hom., cov: 32)
• Consequence: LSAMP ENST00000474851.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LSAMP	ENST00000474851.1	c.178+169742T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34364 AN: 151808 Hom.: 3917 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.226 AC: 34367 AN: 151926 Hom.: 3916 Cov.: 32 AF XY: 0.227 AC XY: 16845 AN XY: 74248

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.219

Alfa AF: 0.202 Hom.: 1889

Bravo AF: 0.227

Asia WGS AF: 0.207 AC: 722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6438347; hg19: chr3-116558335;