3-116465639-C-T

Variant summary

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

The ENST00000474851.1(LSAMP):c.179-20684G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 151,866 control chromosomes in the GnomAD database, including 39,108 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 0.71 (39108 hom., cov: 31)
• Consequence: LSAMP ENST00000474851.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.806 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.179-20684G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108294 AN: 151750 Hom.: 39115 Cov.: 31

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.864

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.827

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.751

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

GnomAD4 genome AF: 0.713 AC: 108304 AN: 151866 Hom.: 39108 Cov.: 31 AF XY: 0.710 AC XY: 52731 AN XY: 74226

Gnomad4 AFR AF: 0.589

Gnomad4 AMR AF: 0.748

Gnomad4 ASJ AF: 0.762

Gnomad4 EAS AF: 0.827

Gnomad4 SAS AF: 0.755

Gnomad4 FIN AF: 0.684

Gnomad4 NFE AF: 0.767

Gnomad4 OTH AF: 0.747

Alfa AF: 0.743 Hom.: 21892

Bravo AF: 0.712

Asia WGS AF: 0.755 AC: 2619 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.42
Dann	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6787168; hg19: chr3-116184486;