ENST00000474851.1:c.178+254933A>C

Variant names:

• chr3-116754297-T-G
• rs6438336
• ENST00000474851.1:c.178+254933A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000474851.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSAMP	ENST00000474851.1	TSL:5	c.178+254933A>C		intron	N/A	ENSP00000418506.1	C9J5G3
	LSAMP	ENST00000717962.1		n.686+254985A>C		intron	N/A

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

African (AFR) AF: 0.851 AC: 35291 AN: 41486

American (AMR) AF: 0.893 AC: 13640 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.996 AC: 3456 AN: 3470

East Asian (EAS) AF: 0.967 AC: 4991 AN: 5162

South Asian (SAS) AF: 0.952 AC: 4583 AN: 4814

European-Finnish (FIN) AF: 0.994 AC: 10533 AN: 10592

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.996 AC: 67760 AN: 68022

Other (OTH) AF: 0.946 AC: 1999 AN: 2114

Alfa AF: 0.939 Hom.: 5765

Bravo AF: 0.930

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.68
DANN	Benign	0.39
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6438336; hg19: chr3-116473144;