3-116462178-A-C

Variant names:

• chr3-116462178-A-C
• rs16824957
• ENST00000474851.1:c.179-17223T>G

Variant summary

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

The ENST00000474851.1(LSAMP):​c.179-17223T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0508 in 152,208 control chromosomes in the GnomAD database, including 241 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 0.051 (241 hom., cov: 31)
• Consequence: LSAMP ENST00000474851.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.478
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0685 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.179-17223T>G		intron	N/A	ENSP00000418506.1
	LSAMP	ENST00000717962.1		n.687-17223T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0508 AC: 7728 AN: 152090 Hom.: 240 Cov.: 31

Gnomad AFR AF: 0.0279

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.0386

Gnomad ASJ AF: 0.0694

Gnomad EAS AF: 0.0405

Gnomad SAS AF: 0.0592

Gnomad FIN AF: 0.0314

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0701

Gnomad OTH AF: 0.0537

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

GnomAD4 genome AF: 0.0508 AC: 7736 AN: 152208 Hom.: 241 Cov.: 31 AF XY: 0.0492 AC XY: 3664 AN XY: 74412

African (AFR) AF: 0.0278 AC: 1155 AN: 41560

American (AMR) AF: 0.0386 AC: 589 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0694 AC: 241 AN: 3472

East Asian (EAS) AF: 0.0408 AC: 211 AN: 5174

South Asian (SAS) AF: 0.0595 AC: 287 AN: 4826

European-Finnish (FIN) AF: 0.0314 AC: 333 AN: 10610

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0702 AC: 4771 AN: 67990

Other (OTH) AF: 0.0555 AC: 117 AN: 2108

Alfa AF: 0.0589 Hom.: 94

Bravo AF: 0.0500

Asia WGS AF: 0.0490 AC: 171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.5
DANN	Benign	0.73
PhyloP100		0.48
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: rs16824957; hg19: chr3-116181025;