3-116246801-C-T

Position:

• chr3-116246801-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.156-160245G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 151,960 control chromosomes in the GnomAD database, including 27,484 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 0.55 (27484 hom., cov: 32)
• Consequence: LSAMP NM_002338.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LSAMP	NM_002338.5	c.156-160245G>A		intron_variant		ENST00000490035.7	NP_002329.2
LSAMP	NM_001318915.2	c.156-160245G>A		intron_variant			NP_001305844.1
LSAMP	XM_017006383.3	c.156-160245G>A		intron_variant			XP_016861872.1
LSAMP	XM_011512840.4	c.156-160245G>A		intron_variant			XP_011511142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LSAMP	ENST00000490035.7	c.156-160245G>A		intron_variant		1	NM_002338.5	ENSP00000419000.1
LSAMP	ENST00000333617.8	c.108-160245G>A		intron_variant		2		ENSP00000328455.4
LSAMP	ENST00000474851.1	c.258-160245G>A		intron_variant		5		ENSP00000418506.1

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83515 AN: 151842 Hom.: 27483 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.550 AC: 83508 AN: 151960 Hom.: 27484 Cov.: 32 AF XY: 0.553 AC XY: 41093 AN XY: 74288

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.608

Gnomad4 ASJ AF: 0.770

Gnomad4 EAS AF: 0.752

Gnomad4 SAS AF: 0.782

Gnomad4 FIN AF: 0.646

Gnomad4 NFE AF: 0.712

Gnomad4 OTH AF: 0.591

Alfa AF: 0.689 Hom.: 78168

Bravo AF: 0.523

Asia WGS AF: 0.723 AC: 2513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.29

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: rs9874470; hg19: chr3-115965648;