rs12629904

Variant names:

• chr3-117511776-C-T
• rs12629904
• XR_007096021.1:n.28456C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_007096021.1(LOC105374056):​n.28456C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0528 in 152,006 control chromosomes in the GnomAD database, including 443 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 0.053 (443 hom., cov: 31)
• Consequence: LOC105374056 XR_007096021.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 2 publications found

Genes affected

LOC105374056 (HGNC:):

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 = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105374056	XR_007096021.1	n.28456C>T		non_coding_transcript_exon_variant	Exon 1 of 3
LOC105374056	XR_924361.3	n.28456C>T		non_coding_transcript_exon_variant	Exon 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSAMP	ENST00000717962.1	n.536-171989G>A		intron_variant	Intron 2 of 6

Frequencies

GnomAD3 genomes AF: 0.0527 AC: 8003 AN: 151888 Hom.: 442 Cov.: 31

Gnomad AFR AF: 0.0122

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0234

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.0574

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0398

Gnomad OTH AF: 0.0442

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

GnomAD4 genome AF: 0.0528 AC: 8019 AN: 152006 Hom.: 443 Cov.: 31 AF XY: 0.0591 AC XY: 4389 AN XY: 74286

African (AFR) AF: 0.0122 AC: 504 AN: 41480

American (AMR) AF: 0.116 AC: 1764 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0234 AC: 81 AN: 3468

East Asian (EAS) AF: 0.218 AC: 1119 AN: 5140

South Asian (SAS) AF: 0.0572 AC: 275 AN: 4808

European-Finnish (FIN) AF: 0.136 AC: 1432 AN: 10554

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0398 AC: 2705 AN: 67988

Other (OTH) AF: 0.0475 AC: 100 AN: 2104

Alfa AF: 0.0455 Hom.: 134

Bravo AF: 0.0519

Asia WGS AF: 0.133 AC: 460 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	0.31
DANN	Benign	0.66
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: rs12629904; hg19: chr3-117230623;