rs2100807

Positions:

• chr3-116305143-C-T

Variant summary

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

The NM_002338.5(LSAMP):​c.155+139734G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 151,990 control chromosomes in the GnomAD database, including 41,746 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 0.72 (41746 hom., cov: 31)
• Consequence: LSAMP NM_002338.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LSAMP	NM_002338.5	c.155+139734G>A		intron_variant		ENST00000490035.7	NP_002329.2
LSAMP	NM_001318915.2	c.155+139734G>A		intron_variant			NP_001305844.1
LSAMP	XM_011512840.4	c.155+139734G>A		intron_variant			XP_011511142.1
LSAMP	XM_017006383.3	c.155+139734G>A		intron_variant			XP_016861872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LSAMP	ENST00000490035.7	c.155+139734G>A		intron_variant		1	NM_002338.5	ENSP00000419000	P1
LSAMP	ENST00000333617.8	c.107+139734G>A		intron_variant		2		ENSP00000328455
LSAMP	ENST00000474851.1	c.257+139734G>A		intron_variant		5		ENSP00000418506

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109244 AN: 151872 Hom.: 41734 Cov.: 31

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.821

Gnomad FIN AF: 0.886

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.820

Gnomad OTH AF: 0.711

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

GnomAD4 genome AF: 0.719 AC: 109290 AN: 151990 Hom.: 41746 Cov.: 31 AF XY: 0.727 AC XY: 54024 AN XY: 74318

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.809

Gnomad4 ASJ AF: 0.752

Gnomad4 EAS AF: 0.910

Gnomad4 SAS AF: 0.822

Gnomad4 FIN AF: 0.886

Gnomad4 NFE AF: 0.820

Gnomad4 OTH AF: 0.712

Alfa AF: 0.797 Hom.: 65248

Bravo AF: 0.699

Asia WGS AF: 0.821 AC: 2856 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.66

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: rs2100807; hg19: chr3-116023990;