rs10511352

Positions:

• chr3-115924430-A-C

Variant summary

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

The NM_002338.5(LSAMP):​c.515-71813T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0745 in 152,256 control chromosomes in the GnomAD database, including 570 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 0.075 (570 hom., cov: 32)
• Consequence: LSAMP NM_002338.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.550

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LSAMP	NM_002338.5	c.515-71813T>G		intron_variant		ENST00000490035.7
LOC124906269	XR_007096010.1	n.59-82706A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LSAMP	ENST00000490035.7	c.515-71813T>G		intron_variant		1	NM_002338.5	P1
LSAMP	ENST00000333617.8	c.467-71813T>G		intron_variant		2
LSAMP	ENST00000498645.1	n.224-71813T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0746 AC: 11354 AN: 152138 Hom.: 571 Cov.: 32

Gnomad AFR AF: 0.0194

Gnomad AMI AF: 0.0857

Gnomad AMR AF: 0.0798

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0700

Gnomad SAS AF: 0.0845

Gnomad FIN AF: 0.0938

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0989

Gnomad OTH AF: 0.0979

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

GnomAD4 genome AF: 0.0745 AC: 11350 AN: 152256 Hom.: 570 Cov.: 32 AF XY: 0.0739 AC XY: 5503 AN XY: 74436

Gnomad4 AFR AF: 0.0194

Gnomad4 AMR AF: 0.0797

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.0698

Gnomad4 SAS AF: 0.0840

Gnomad4 FIN AF: 0.0938

Gnomad4 NFE AF: 0.0988

Gnomad4 OTH AF: 0.0997

Alfa AF: 0.0977 Hom.: 833

Bravo AF: 0.0723

Asia WGS AF: 0.0950 AC: 330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.67
DANN	Benign	0.77

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: rs10511352; hg19: chr3-115643277;