rs2918217

Positions:

• chr3-115827533-C-T

Variant summary

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

The NM_002338.5(LSAMP):​c.919+14312G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 151,946 control chromosomes in the GnomAD database, including 5,495 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 0.24 (5495 hom., cov: 31)
• Consequence: LSAMP NM_002338.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111

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]

LOC124906269 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LSAMP	NM_002338.5	c.919+14312G>A		intron_variant		ENST00000490035.7	NP_002329.2
LOC124906269	XR_007096010.1	n.58+36375C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LSAMP	ENST00000490035.7	c.919+14312G>A		intron_variant		1	NM_002338.5	ENSP00000419000	P1
LSAMP	ENST00000333617.8	c.907+7029G>A		intron_variant		2		ENSP00000328455
LSAMP	ENST00000475403.2	n.225+7029G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36010 AN: 151828 Hom.: 5455 Cov.: 31

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.238 AC: 36118 AN: 151946 Hom.: 5495 Cov.: 31 AF XY: 0.239 AC XY: 17780 AN XY: 74262

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.232

Alfa AF: 0.165 Hom.: 1960

Bravo AF: 0.262

Asia WGS AF: 0.217 AC: 754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.2
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2918217; hg19: chr3-115546380;