rs2269350

Positions:

chr3-39411669-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.450

Variant links:

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]

RPSA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
RPSA	NM_002295.6 linkuse as main transcript	c.519G>A	p.Leu173=	synonymous_variant	5/7	ENST00000301821.11	NP_002286.2
RPSA	NM_001304288.2 linkuse as main transcript	c.534G>A	p.Leu178=	synonymous_variant	5/7		NP_001291217.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPSA	ENST00000301821.11 linkuse as main transcript	c.519G>A	p.Leu173=	synonymous_variant	5/7	1	NM_002295.6	ENSP00000346067	P4

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40671

AN:

151982

Hom.:

6010

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.310

AC XY:

224477

AN XY:

724198

show subpopulations

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.:

AF XY:

0.267

AC XY:

19885

AN XY:

74364

show subpopulations

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:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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 -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over