chr3-116233952-T-C

Variant names:

• chr3-116233952-T-C
• rs1870709
• NM_002338.5:c.156-147396A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002338.5(LSAMP):​c.156-147396A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 152,084 control chromosomes in the GnomAD database, including 40,722 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 0.72 (40722 hom., cov: 32)
• Consequence: LSAMP NM_002338.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• Publications: 5 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002338.5. 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
	LSAMP	NM_002338.5	MANE Select	c.156-147396A>G		intron	N/A	NP_002329.2
	LSAMP	NM_001318915.2		c.156-147396A>G		intron	N/A	NP_001305844.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSAMP	ENST00000490035.7	TSL:1 MANE Select	c.156-147396A>G		intron	N/A	ENSP00000419000.1
	LSAMP	ENST00000333617.8	TSL:2	c.108-147396A>G		intron	N/A	ENSP00000328455.4
	LSAMP	ENST00000474851.1	TSL:5	c.258-147396A>G		intron	N/A	ENSP00000418506.1

Frequencies

GnomAD3 genomes AF: 0.718 AC: 109063 AN: 151966 Hom.: 40721 Cov.: 32

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.883

Gnomad EAS AF: 0.791

Gnomad SAS AF: 0.842

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.822

Gnomad OTH AF: 0.751

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

GnomAD4 genome AF: 0.717 AC: 109082 AN: 152084 Hom.: 40722 Cov.: 32 AF XY: 0.715 AC XY: 53188 AN XY: 74338

African (AFR) AF: 0.497 AC: 20594 AN: 41446

American (AMR) AF: 0.731 AC: 11176 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.883 AC: 3067 AN: 3472

East Asian (EAS) AF: 0.790 AC: 4090 AN: 5174

South Asian (SAS) AF: 0.842 AC: 4058 AN: 4818

European-Finnish (FIN) AF: 0.722 AC: 7641 AN: 10580

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.822 AC: 55900 AN: 68000

Other (OTH) AF: 0.751 AC: 1587 AN: 2112

Alfa AF: 0.792 Hom.: 195737

Bravo AF: 0.704

Asia WGS AF: 0.790 AC: 2746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	20
DANN	Benign	0.84
PhyloP100		1.2
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: rs1870709; hg19: chr3-115952799;