rs6438308

Positions:

• chr3-116235627-C-G
• chr3-116235627-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.156-149071G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 152,092 control chromosomes in the GnomAD database, including 40,424 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 0.71 (40424 hom., cov: 33)
• Consequence: LSAMP NM_002338.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.367

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 (SAS) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LSAMP	NM_002338.5	c.156-149071G>C		intron_variant		ENST00000490035.7
LSAMP	NM_001318915.2	c.156-149071G>C		intron_variant
LSAMP	XM_011512840.4	c.156-149071G>C		intron_variant
LSAMP	XM_017006383.3	c.156-149071G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LSAMP	ENST00000490035.7	c.156-149071G>C		intron_variant		1	NM_002338.5	P1
LSAMP	ENST00000333617.8	c.108-149071G>C		intron_variant		2
LSAMP	ENST00000474851.1	c.258-149071G>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108501 AN: 151974 Hom.: 40425 Cov.: 33

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.883

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.841

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.822

Gnomad OTH AF: 0.747

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

GnomAD4 genome AF: 0.713 AC: 108517 AN: 152092 Hom.: 40424 Cov.: 33 AF XY: 0.712 AC XY: 52930 AN XY: 74346

Gnomad4 AFR AF: 0.484

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.883

Gnomad4 EAS AF: 0.792

Gnomad4 SAS AF: 0.841

Gnomad4 FIN AF: 0.722

Gnomad4 NFE AF: 0.822

Gnomad4 OTH AF: 0.748

Alfa AF: 0.756 Hom.: 5562

Bravo AF: 0.700

Asia WGS AF: 0.786 AC: 2735 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	1.8
DANN	Benign	0.34

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: rs6438308; hg19: chr3-115954474;