rs2269350

chr3-39411669-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_002295.6(RPSA):c.519G>A(p.Leu173=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 1,607,196 control chromosomes in the GnomAD database, including 77,234 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (6021 hom., cov: 32)
  • Exomes 𝑓: 0.31 (71213 hom.)
• Consequence: RPSA NM_002295.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.450

Genes affected

RPSA (HGNC:6502): (ribosomal protein SA) Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Many of the effects of laminin are mediated through interactions with cell surface receptors. These receptors include members of the integrin family, as well as non-integrin laminin-binding proteins. This gene encodes a high-affinity, non-integrin family, laminin receptor 1. This receptor has been variously called 67 kD laminin receptor, 37 kD laminin receptor precursor (37LRP) and p40 ribosome-associated protein. The amino acid sequence of laminin receptor 1 is highly conserved through evolution, suggesting a key biological function. It has been observed that the level of the laminin receptor transcript is higher in colon carcinoma tissue and lung cancer cell line than their normal counterparts. Also, there is a correlation between the upregulation of this polypeptide in cancer cells and their invasive and metastatic phenotype. Multiple copies of this gene exist, however, most of them are pseudogenes thought to have arisen from retropositional events. Two alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 3-39411669-G-A is Benign according to our data. Variant chr3-39411669-G-A is described in ClinVar as [Benign]. Clinvar id is 403396.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.45 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPSA	NM_002295.6	c.519G>A	p.Leu173=	synonymous_variant	5/7	ENST00000301821.11
RPSA	NM_001304288.2	c.534G>A	p.Leu178=	synonymous_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPSA	ENST00000301821.11	c.519G>A	p.Leu173=	synonymous_variant	5/7	1	NM_002295.6	P4

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40671 AN: 151982 Hom.: 6010 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.262

GnomAD3 exomes AF: 0.293 AC: 72494 AN: 246998 Hom.: 11000 AF XY: 0.296 AC XY: 39622 AN XY: 133910

Gnomad AFR exome AF: 0.157

Gnomad AMR exome AF: 0.288

Gnomad ASJ exome AF: 0.363

Gnomad EAS exome AF: 0.250

Gnomad SAS exome AF: 0.270

Gnomad FIN exome AF: 0.298

Gnomad NFE exome AF: 0.321

Gnomad OTH exome AF: 0.302

GnomAD4 exome AF: 0.311 AC: 452766 AN: 1455096 Hom.: 71213 Cov.: 41 AF XY: 0.310 AC XY: 224477 AN XY: 724198

Gnomad4 AFR exome AF: 0.153

Gnomad4 AMR exome AF: 0.286

Gnomad4 ASJ exome AF: 0.361

Gnomad4 EAS exome AF: 0.290

Gnomad4 SAS exome AF: 0.274

Gnomad4 FIN exome AF: 0.295

Gnomad4 NFE exome AF: 0.321

Gnomad4 OTH exome AF: 0.305

GnomAD4 genome AF: 0.268 AC: 40695 AN: 152100 Hom.: 6021 Cov.: 32 AF XY: 0.267 AC XY: 19885 AN XY: 74364

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.262

Alfa AF: 0.307 Hom.: 1667

Bravo AF: 0.260

Asia WGS AF: 0.259 AC: 901 AN: 3478

EpiCase AF: 0.306

EpiControl AF: 0.318

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Familial isolated congenital asplenia Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	8.6
Dann	Benign	0.90

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: rs2269350; hg19: chr3-39453160; COSMIC: COSV57191059; COSMIC: COSV57191059;