3-115846523-T-C

Variant names:

• chr3-115846523-T-C
• rs4416377
• NM_002338.5:c.650-3945A>G

Variant summary

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

The NM_002338.5(LSAMP):​c.650-3945A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,210 control chromosomes in the GnomAD database, including 3,626 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 0.21 (3626 hom., cov: 32)
• Consequence: LSAMP NM_002338.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.659
• 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]

ENSG00000297708 (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 (AFR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LSAMP	NM_002338.5	c.650-3945A>G		intron_variant	Intron 4 of 6	ENST00000490035.7	NP_002329.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSAMP	ENST00000490035.7	c.650-3945A>G		intron_variant	Intron 4 of 6	1	NM_002338.5	ENSP00000419000.1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32623 AN: 152092 Hom.: 3620 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.0681

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.214 AC: 32639 AN: 152210 Hom.: 3626 Cov.: 32 AF XY: 0.208 AC XY: 15454 AN XY: 74434

African (AFR) AF: 0.246 AC: 10207 AN: 41506

American (AMR) AF: 0.182 AC: 2780 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 732 AN: 3468

East Asian (EAS) AF: 0.0679 AC: 352 AN: 5186

South Asian (SAS) AF: 0.150 AC: 724 AN: 4834

European-Finnish (FIN) AF: 0.143 AC: 1517 AN: 10604

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15566 AN: 68010

Other (OTH) AF: 0.221 AC: 467 AN: 2112

Alfa AF: 0.214 Hom.: 483

Bravo AF: 0.218

Asia WGS AF: 0.126 AC: 443 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.2
DANN	Benign	0.68
PhyloP100		0.66
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4416377; hg19: chr3-115565370;