chr3-116453893-T-A

Variant names:

• chr3-116453893-T-A
• rs4831140
• ENST00000474851.1:c.179-8938A>T

Variant summary

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

The ENST00000474851.1(LSAMP):​c.179-8938A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 152,044 control chromosomes in the GnomAD database, including 49,751 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 0.80 (49751 hom., cov: 31)
• Consequence: LSAMP ENST00000474851.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.336

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=-0.66).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSAMP	ENST00000474851.1	c.179-8938A>T		intron_variant	Intron 2 of 4	5		ENSP00000418506.1

Frequencies

GnomAD3 genomes AF: 0.802 AC: 121874 AN: 151926 Hom.: 49755 Cov.: 31

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.881

Gnomad AMR AF: 0.816

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.920

Gnomad SAS AF: 0.936

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.876

Gnomad OTH AF: 0.841

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

GnomAD4 genome AF: 0.802 AC: 121896 AN: 152044 Hom.: 49751 Cov.: 31 AF XY: 0.799 AC XY: 59414 AN XY: 74332

Gnomad4 AFR AF: 0.641

Gnomad4 AMR AF: 0.815

Gnomad4 ASJ AF: 0.887

Gnomad4 EAS AF: 0.920

Gnomad4 SAS AF: 0.936

Gnomad4 FIN AF: 0.767

Gnomad4 NFE AF: 0.876

Gnomad4 OTH AF: 0.839

Alfa AF: 0.754 Hom.: 2334

Bravo AF: 0.795

Asia WGS AF: 0.886 AC: 3082 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.9
DANN	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4831140; hg19: chr3-116172740;