3-116227026-C-T

Variant names:

• chr3-116227026-C-T
• rs4831124
• NM_002338.5:c.156-140470G>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.156-140470G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 151,820 control chromosomes in the GnomAD database, including 29,625 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 0.62 (29625 hom., cov: 32)
• Consequence: LSAMP NM_002338.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.692
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LSAMP	NM_002338.5	c.156-140470G>A		intron_variant	Intron 1 of 6	ENST00000490035.7	NP_002329.2
LSAMP	NM_001318915.2	c.156-140470G>A		intron_variant	Intron 1 of 8		NP_001305844.1
LSAMP	XM_017006383.3	c.156-140470G>A		intron_variant	Intron 1 of 7		XP_016861872.1
LSAMP	XM_011512840.4	c.156-140470G>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.156-140470G>A		intron_variant	Intron 1 of 6	1	NM_002338.5	ENSP00000419000.1
LSAMP	ENST00000333617.8	c.108-140470G>A		intron_variant	Intron 1 of 8	2		ENSP00000328455.4
LSAMP	ENST00000474851.1	c.258-140470G>A		intron_variant	Intron 3 of 4	5		ENSP00000418506.1
LSAMP	ENST00000717962.1	n.766-140470G>A		intron_variant	Intron 5 of 6

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94061 AN: 151702 Hom.: 29621 Cov.: 32

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.713

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.658

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

GnomAD4 genome AF: 0.620 AC: 94102 AN: 151820 Hom.: 29625 Cov.: 32 AF XY: 0.619 AC XY: 45906 AN XY: 74202

African (AFR) AF: 0.489 AC: 20234 AN: 41362

American (AMR) AF: 0.619 AC: 9455 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 2437 AN: 3468

East Asian (EAS) AF: 0.776 AC: 4011 AN: 5170

South Asian (SAS) AF: 0.714 AC: 3442 AN: 4818

European-Finnish (FIN) AF: 0.638 AC: 6713 AN: 10518

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.671 AC: 45554 AN: 67914

Other (OTH) AF: 0.659 AC: 1388 AN: 2106

Alfa AF: 0.656 Hom.: 121282

Bravo AF: 0.609

Asia WGS AF: 0.726 AC: 2523 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.9
DANN	Benign	0.20
PhyloP100		0.69
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: rs4831124; hg19: chr3-115945873;