rs2269350

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002295.6(RPSA):c.519G>A(p.Leu173Leu) 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

Publications

23 publications found

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 Gene-Disease associations (from GenCC):

familial isolated congenital asplenia
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

RPSA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002295.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPSA	NM_002295.6	MANE Select	c.519G>A	p.Leu173Leu	synonymous	Exon 5 of 7	NP_002286.2
	RPSA	NM_001304288.2		c.534G>A	p.Leu178Leu	synonymous	Exon 5 of 7	NP_001291217.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RPSA	ENST00000301821.11	TSL:1 MANE Select	c.519G>A	p.Leu173Leu	synonymous	Exon 5 of 7	ENSP00000346067.4
RPSA	ENST00000443003.2	TSL:1	c.534G>A	p.Leu178Leu	synonymous	Exon 5 of 7	ENSP00000389351.1
RPSA	ENST00000495394.2	TSL:1	n.2459G>A		non_coding_transcript_exon	Exon 1 of 2

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

GnomAD2 exomes

AF:

0.293

AC:

72494

AN:

246998

AF XY:

0.296

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 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

African (AFR)

AF:

0.153

AC:

5120

AN:

33472

American (AMR)

AF:

0.286

AC:

12799

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.361

AC:

9436

AN:

26124

East Asian (EAS)

AF:

0.290

AC:

11494

AN:

39692

South Asian (SAS)

AF:

0.274

AC:

23604

AN:

86238

European-Finnish (FIN)

AF:

0.295

AC:

13918

AN:

47256

Middle Eastern (MID)

AF:

0.243

AC:

1395

AN:

5746

European-Non Finnish (NFE)

AF:

0.321

AC:

356604

AN:

1111582

Other (OTH)

AF:

0.305

AC:

18396

AN:

60304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

16544

33087

49631

66174

82718

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11568

23136

34704

46272

57840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.268

AC:

40695

AN:

152100

Hom.:

6021

Cov.:

AF XY:

0.267

AC XY:

19885

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.160

AC:

6658

AN:

41498

American (AMR)

AF:

0.287

AC:

4384

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.355

AC:

1232

AN:

3472

East Asian (EAS)

AF:

0.274

AC:

1415

AN:

5164

South Asian (SAS)

AF:

0.281

AC:

1355

AN:

4818

European-Finnish (FIN)

AF:

0.296

AC:

3127

AN:

10572

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.319

AC:

21713

AN:

67976

Other (OTH)

AF:

0.262

AC:

552

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1482

2964

4446

5928

7410

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

412

824

1236

1648

2060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.303

Hom.:

1681

Bravo

AF:

0.260

Asia WGS

AF:

0.259

AC:

901

AN:

3478

EpiCase

AF:

0.306

EpiControl

AF:

0.318

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Familial isolated congenital asplenia (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

8.6

(source)

DANN

Benign

0.90

PhyloP100

0.45

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over