3-116726477-T-G

Position:

• chr3-116726477-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.116726477T>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LSAMP	ENST00000474851.1	c.179-281522A>C		intron_variant		5		ENSP00000418506.1

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

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.526

Gnomad4 ASJ AF: 0.601

Gnomad4 EAS AF: 0.685

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.501

Alfa AF: 0.453 Hom.: 2272

Bravo AF: 0.471

Asia WGS AF: 0.550 AC: 1913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.6
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1432364; hg19: chr3-116445324;