rs9289051

Variant names:

• chr3-116398759-G-T
• rs9289051
• NM_002338.5:c.155+46118C>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.155+46118C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,136 control chromosomes in the GnomAD database, including 3,495 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 0.19 (3495 hom., cov: 32)
• Consequence: LSAMP NM_002338.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.297
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LSAMP	NM_002338.5	c.155+46118C>A		intron_variant	Intron 1 of 6	ENST00000490035.7	NP_002329.2
LSAMP	NM_001318915.2	c.155+46118C>A		intron_variant	Intron 1 of 8		NP_001305844.1
LSAMP	XM_017006383.3	c.155+46118C>A		intron_variant	Intron 1 of 7		XP_016861872.1
LSAMP	XM_011512840.4	c.155+46118C>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.155+46118C>A		intron_variant	Intron 1 of 6	1	NM_002338.5	ENSP00000419000.1
LSAMP	ENST00000333617.8	c.107+46118C>A		intron_variant	Intron 1 of 8	2		ENSP00000328455.4
LSAMP	ENST00000474851.1	c.257+46118C>A		intron_variant	Intron 3 of 4	5		ENSP00000418506.1
LSAMP	ENST00000717962.1	n.765+46118C>A		intron_variant	Intron 5 of 6

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28449 AN: 152020 Hom.: 3495 Cov.: 32

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.0663

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.187 AC: 28455 AN: 152136 Hom.: 3495 Cov.: 32 AF XY: 0.182 AC XY: 13506 AN XY: 74386

African (AFR) AF: 0.351 AC: 14550 AN: 41462

American (AMR) AF: 0.170 AC: 2598 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 699 AN: 3472

East Asian (EAS) AF: 0.135 AC: 699 AN: 5176

South Asian (SAS) AF: 0.169 AC: 814 AN: 4822

European-Finnish (FIN) AF: 0.0663 AC: 703 AN: 10596

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7794 AN: 68000

Other (OTH) AF: 0.189 AC: 399 AN: 2108

Alfa AF: 0.150 Hom.: 496

Bravo AF: 0.201

Asia WGS AF: 0.173 AC: 600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.45
DANN	Benign	0.74
PhyloP100		-0.30
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: rs9289051; hg19: chr3-116117606;