rs4258973

Variant names:

• chr3-116916241-C-A
• rs4258973
• ENST00000474851.1:c.178+92989G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-116916241-C-A
• chr3-116916241-C-G

Variant summary

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

The ENST00000474851.1(LSAMP):​c.178+92989G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 151,972 control chromosomes in the GnomAD database, including 8,546 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 0.32 (8546 hom., cov: 32)
• Consequence: LSAMP ENST00000474851.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 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+92989G>T		intron_variant	Intron 2 of 4	5		ENSP00000418506.1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48808 AN: 151854 Hom.: 8536 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.321 AC: 48857 AN: 151972 Hom.: 8546 Cov.: 32 AF XY: 0.320 AC XY: 23737 AN XY: 74282

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.301

Alfa AF: 0.139 Hom.: 226

Bravo AF: 0.330

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	9.8
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4258973; hg19: chr3-116635088;