chr3-116754297-T-G

Position:

• chr3-116754297-T-G

Variant summary

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

The ENST00000474851.1(LSAMP):​c.178+254933A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.943 in 152,136 control chromosomes in the GnomAD database, including 67,989 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 0.94 (67989 hom., cov: 31)
• Consequence: LSAMP ENST00000474851.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.116754297T>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LSAMP	ENST00000474851.1	c.178+254933A>C		intron_variant		5		ENSP00000418506.1

Frequencies

GnomAD3 genomes AF: 0.943 AC: 143371 AN: 152018 Hom.: 67960 Cov.: 31

Gnomad AFR AF: 0.851

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.894

Gnomad ASJ AF: 0.996

Gnomad EAS AF: 0.967

Gnomad SAS AF: 0.952

Gnomad FIN AF: 0.994

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.996

Gnomad OTH AF: 0.946

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

GnomAD4 genome AF: 0.943 AC: 143454 AN: 152136 Hom.: 67989 Cov.: 31 AF XY: 0.942 AC XY: 70106 AN XY: 74390

Gnomad4 AFR AF: 0.851

Gnomad4 AMR AF: 0.893

Gnomad4 ASJ AF: 0.996

Gnomad4 EAS AF: 0.967

Gnomad4 SAS AF: 0.952

Gnomad4 FIN AF: 0.994

Gnomad4 NFE AF: 0.996

Gnomad4 OTH AF: 0.946

Alfa AF: 0.947 Hom.: 5511

Bravo AF: 0.930

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.68
DANN	Benign	0.39

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6438336; hg19: chr3-116473144;