rs2937673

Variant names:

• chr3-117513540-A-G
• rs2937673
• ENST00000717962.1:n.536-173753T>C

Variant summary

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

The ENST00000717962.1(LSAMP):​n.536-173753T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 151,986 control chromosomes in the GnomAD database, including 14,789 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 0.40 (14789 hom., cov: 31)
• Consequence: LSAMP ENST00000717962.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.27
• Publications: 3 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]

ENSG00000303790 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105374056	XR_007096021.1	n.30023+197A>G		intron_variant	Intron 1 of 2
LOC105374056	XR_924361.3	n.30023+197A>G		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSAMP	ENST00000717962.1	n.536-173753T>C		intron_variant	Intron 2 of 6
ENSG00000303790	ENST00000797238.1	n.116+197A>G		intron_variant	Intron 1 of 5
ENSG00000303790	ENST00000797242.1	n.148+197A>G		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60481 AN: 151870 Hom.: 14794 Cov.: 31

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.418

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

GnomAD4 genome AF: 0.398 AC: 60458 AN: 151986 Hom.: 14789 Cov.: 31 AF XY: 0.392 AC XY: 29137 AN XY: 74270

African (AFR) AF: 0.128 AC: 5321 AN: 41498

American (AMR) AF: 0.332 AC: 5055 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1791 AN: 3462

East Asian (EAS) AF: 0.225 AC: 1160 AN: 5160

South Asian (SAS) AF: 0.449 AC: 2164 AN: 4818

European-Finnish (FIN) AF: 0.498 AC: 5249 AN: 10548

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.565 AC: 38349 AN: 67934

Other (OTH) AF: 0.413 AC: 874 AN: 2114

Alfa AF: 0.402 Hom.: 8316

Bravo AF: 0.370

Asia WGS AF: 0.325 AC: 1134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.59
PhyloP100		2.3
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: rs2937673; hg19: chr3-117232387;