rs2868975

Variant names:

• chr3-117216476-G-A
• rs2868975
• ENST00000717962.1:n.593+123254C>T

Variant summary

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

The ENST00000717962.1(LSAMP):​n.593+123254C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 151,856 control chromosomes in the GnomAD database, including 2,773 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 0.19 (2773 hom., cov: 32)
• Consequence: LSAMP ENST00000717962.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.109
• Publications: 7 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]

LOC124909415 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124909415	XR_007096015.1	n.29329+32540C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSAMP	ENST00000717962.1	n.593+123254C>T		intron_variant	Intron 3 of 6

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28894 AN: 151738 Hom.: 2777 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.190 AC: 28905 AN: 151856 Hom.: 2773 Cov.: 32 AF XY: 0.192 AC XY: 14272 AN XY: 74222

African (AFR) AF: 0.194 AC: 8038 AN: 41444

American (AMR) AF: 0.183 AC: 2791 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 702 AN: 3462

East Asian (EAS) AF: 0.190 AC: 979 AN: 5162

South Asian (SAS) AF: 0.242 AC: 1162 AN: 4810

European-Finnish (FIN) AF: 0.232 AC: 2442 AN: 10528

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12195 AN: 67922

Other (OTH) AF: 0.200 AC: 421 AN: 2106

Alfa AF: 0.183 Hom.: 1438

Bravo AF: 0.184

Asia WGS AF: 0.222 AC: 768 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.6
DANN	Benign	0.52
PhyloP100		0.11
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: rs2868975; hg19: chr3-116935323;