rs2289271

Positions:

• chr3-115809913-C-T

Variant summary

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

The NM_002338.5(LSAMP):​c.*404G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 157,816 control chromosomes in the GnomAD database, including 24,127 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 0.54 (23688 hom., cov: 31)
  • Exomes 𝑓: 0.36 (439 hom.)
• Consequence: LSAMP NM_002338.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.36

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]

LOC124906269 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LSAMP	NM_002338.5	c.*404G>A		3_prime_UTR_variant	7/7	ENST00000490035.7
LOC124906269	XR_007096010.1	n.58+18755C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LSAMP	ENST00000490035.7	c.*404G>A		3_prime_UTR_variant	7/7	1	NM_002338.5	P1
LSAMP	ENST00000333617.8	c.*404G>A		3_prime_UTR_variant	9/9	2

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81257 AN: 151666 Hom.: 23651 Cov.: 31

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.547

GnomAD4 exome AF: 0.360 AC: 2170 AN: 6032 Hom.: 439 Cov.: 0 AF XY: 0.363 AC XY: 1165 AN XY: 3212

Gnomad4 AFR exome AF: 0.759

Gnomad4 AMR exome AF: 0.399

Gnomad4 ASJ exome AF: 0.331

Gnomad4 EAS exome AF: 0.200

Gnomad4 SAS exome AF: 0.265

Gnomad4 FIN exome AF: 0.347

Gnomad4 NFE exome AF: 0.363

Gnomad4 OTH exome AF: 0.362

GnomAD4 genome AF: 0.536 AC: 81334 AN: 151784 Hom.: 23688 Cov.: 31 AF XY: 0.536 AC XY: 39748 AN XY: 74178

Gnomad4 AFR AF: 0.790

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.407

Gnomad4 FIN AF: 0.470

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.543

Alfa AF: 0.447 Hom.: 22380

Bravo AF: 0.550

Asia WGS AF: 0.398 AC: 1387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2289271; hg19: chr3-115528760;