3-116839488-A-G

Variant names:

• chr3-116839488-A-G
• rs6438347
• ENST00000474851.1:c.178+169742T>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+169742T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 151,926 control chromosomes in the GnomAD database, including 3,916 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 0.23 (3916 hom., cov: 32)
• Consequence: LSAMP ENST00000474851.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSAMP	ENST00000474851.1	c.178+169742T>C		intron_variant	Intron 2 of 4	5		ENSP00000418506.1
LSAMP	ENST00000717962.1	n.686+169794T>C		intron_variant	Intron 4 of 6

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34364 AN: 151808 Hom.: 3917 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.226 AC: 34367 AN: 151926 Hom.: 3916 Cov.: 32 AF XY: 0.227 AC XY: 16845 AN XY: 74248

African (AFR) AF: 0.220 AC: 9142 AN: 41462

American (AMR) AF: 0.218 AC: 3316 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1147 AN: 3464

East Asian (EAS) AF: 0.266 AC: 1368 AN: 5136

South Asian (SAS) AF: 0.162 AC: 781 AN: 4822

European-Finnish (FIN) AF: 0.254 AC: 2683 AN: 10574

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 15040 AN: 67918

Other (OTH) AF: 0.219 AC: 462 AN: 2110

Alfa AF: 0.206 Hom.: 2622

Bravo AF: 0.227

Asia WGS AF: 0.207 AC: 722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.50
PhyloP100		0.035
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: rs6438347; hg19: chr3-116558335;