3-116262596-G-T

Variant names:

• chr3-116262596-G-T
• rs4831129
• NM_002338.5:c.156-176040C>A

Variant summary

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

The NM_002338.5(LSAMP):​c.156-176040C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 152,086 control chromosomes in the GnomAD database, including 28,393 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 0.56 (28393 hom., cov: 32)
• Consequence: LSAMP NM_002338.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.278
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LSAMP	NM_002338.5	c.156-176040C>A		intron_variant	Intron 1 of 6	ENST00000490035.7	NP_002329.2
LSAMP	NM_001318915.2	c.156-176040C>A		intron_variant	Intron 1 of 8		NP_001305844.1
LSAMP	XM_017006383.3	c.156-176040C>A		intron_variant	Intron 1 of 7		XP_016861872.1
LSAMP	XM_011512840.4	c.156-176040C>A		intron_variant	Intron 1 of 7		XP_011511142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSAMP	ENST00000490035.7	c.156-176040C>A		intron_variant	Intron 1 of 6	1	NM_002338.5	ENSP00000419000.1
LSAMP	ENST00000333617.8	c.108-176040C>A		intron_variant	Intron 1 of 8	2		ENSP00000328455.4
LSAMP	ENST00000474851.1	c.258-176040C>A		intron_variant	Intron 3 of 4	5		ENSP00000418506.1
LSAMP	ENST00000717962.1	n.766-176040C>A		intron_variant	Intron 5 of 6

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85780 AN: 151966 Hom.: 28389 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.750

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.597

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

GnomAD4 genome AF: 0.564 AC: 85779 AN: 152086 Hom.: 28393 Cov.: 32 AF XY: 0.567 AC XY: 42161 AN XY: 74310

African (AFR) AF: 0.193 AC: 8023 AN: 41476

American (AMR) AF: 0.615 AC: 9401 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 2640 AN: 3470

East Asian (EAS) AF: 0.750 AC: 3877 AN: 5168

South Asian (SAS) AF: 0.767 AC: 3694 AN: 4814

European-Finnish (FIN) AF: 0.652 AC: 6877 AN: 10544

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.724 AC: 49241 AN: 68012

Other (OTH) AF: 0.598 AC: 1265 AN: 2114

Alfa AF: 0.654 Hom.: 84725

Bravo AF: 0.539

Asia WGS AF: 0.722 AC: 2509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.47
PhyloP100		0.28
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: rs4831129; hg19: chr3-115981443;