rs10511351

Positions:

• chr3-115875328-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002338.5(LSAMP):​c.515-22711C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,064 control chromosomes in the GnomAD database, including 1,562 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 0.12 (1562 hom., cov: 32)
• Consequence: LSAMP NM_002338.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.908

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]

LOC124906269 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LSAMP	NM_002338.5	c.515-22711C>T		intron_variant		ENST00000490035.7
LOC124906269	XR_007096010.1	n.58+84170G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LSAMP	ENST00000490035.7	c.515-22711C>T		intron_variant		1	NM_002338.5	P1
LSAMP	ENST00000333617.8	c.467-22711C>T		intron_variant		2
LSAMP	ENST00000498645.1	n.224-22711C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18702 AN: 151946 Hom.: 1563 Cov.: 32

Gnomad AFR AF: 0.0318

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0657

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.123 AC: 18696 AN: 152064 Hom.: 1562 Cov.: 32 AF XY: 0.121 AC XY: 9000 AN XY: 74326

Gnomad4 AFR AF: 0.0317

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.000967

Gnomad4 SAS AF: 0.0653

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.117

Alfa AF: 0.170 Hom.: 3078

Bravo AF: 0.115

Asia WGS AF: 0.0310 AC: 109 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	14
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs10511351; hg19: chr3-115594175;