chr3-116235627-C-G

Variant names:

• chr3-116235627-C-G
• rs6438308
• NM_002338.5:c.156-149071G>C

Variant summary

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

The NM_002338.5(LSAMP):​c.156-149071G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 152,092 control chromosomes in the GnomAD database, including 40,424 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 0.71 (40424 hom., cov: 33)
• Consequence: LSAMP NM_002338.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.367
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.82 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.156-149071G>C		intron	N/A	NP_002329.2
	LSAMP	NM_001318915.2		c.156-149071G>C		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.156-149071G>C		intron	N/A	ENSP00000419000.1
	LSAMP	ENST00000333617.8	TSL:2	c.108-149071G>C		intron	N/A	ENSP00000328455.4
	LSAMP	ENST00000474851.1	TSL:5	c.258-149071G>C		intron	N/A	ENSP00000418506.1

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108501 AN: 151974 Hom.: 40425 Cov.: 33

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.883

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.841

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.822

Gnomad OTH AF: 0.747

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

GnomAD4 genome AF: 0.713 AC: 108517 AN: 152092 Hom.: 40424 Cov.: 33 AF XY: 0.712 AC XY: 52930 AN XY: 74346

African (AFR) AF: 0.484 AC: 20044 AN: 41446

American (AMR) AF: 0.730 AC: 11160 AN: 15288

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

East Asian (EAS) AF: 0.792 AC: 4094 AN: 5170

South Asian (SAS) AF: 0.841 AC: 4060 AN: 4826

European-Finnish (FIN) AF: 0.722 AC: 7634 AN: 10572

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.822 AC: 55909 AN: 67996

Other (OTH) AF: 0.748 AC: 1582 AN: 2116

Alfa AF: 0.756 Hom.: 5562

Bravo AF: 0.700

Asia WGS AF: 0.786 AC: 2735 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.34
PhyloP100		0.37
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: rs6438308; hg19: chr3-115954474;