chr3-39407646-T-C

Position:

• chr3-39407646-T-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_002295.6(RPSA):​c.-8T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 1,581,046 control chromosomes in the GnomAD database, including 193,633 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (19015 hom., cov: 32)
  • Exomes 𝑓: 0.49 (174618 hom.)
• Consequence: RPSA NM_002295.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.34

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 3-39407646-T-C is Benign according to our data. Variant chr3-39407646-T-C is described in ClinVar as [Benign]. Clinvar id is 403395.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPSA	NM_002295.6	c.-8T>C		5_prime_UTR_variant	2/7	ENST00000301821.11
RPSA	NM_001304288.2	c.-8T>C		5_prime_UTR_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPSA	ENST00000301821.11	c.-8T>C		5_prime_UTR_variant	2/7	1	NM_002295.6	P4

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75272 AN: 151926 Hom.: 18981 Cov.: 32

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.491

GnomAD3 exomes AF: 0.460 AC: 107557 AN: 233646 Hom.: 25487 AF XY: 0.460 AC XY: 59049 AN XY: 128450

Gnomad AFR exome AF: 0.524

Gnomad AMR exome AF: 0.427

Gnomad ASJ exome AF: 0.557

Gnomad EAS exome AF: 0.300

Gnomad SAS exome AF: 0.370

Gnomad FIN exome AF: 0.440

Gnomad NFE exome AF: 0.506

Gnomad OTH exome AF: 0.488

GnomAD4 exome AF: 0.489 AC: 699472 AN: 1429002 Hom.: 174618 Cov.: 32 AF XY: 0.486 AC XY: 345893 AN XY: 712156

Gnomad4 AFR exome AF: 0.529

Gnomad4 AMR exome AF: 0.431

Gnomad4 ASJ exome AF: 0.562

Gnomad4 EAS exome AF: 0.334

Gnomad4 SAS exome AF: 0.376

Gnomad4 FIN exome AF: 0.438

Gnomad4 NFE exome AF: 0.505

Gnomad4 OTH exome AF: 0.490

GnomAD4 genome AF: 0.496 AC: 75360 AN: 152044 Hom.: 19015 Cov.: 32 AF XY: 0.489 AC XY: 36346 AN XY: 74318

Gnomad4 AFR AF: 0.533

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.560

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.508

Gnomad4 OTH AF: 0.490

Alfa AF: 0.507 Hom.: 5112

Bravo AF: 0.498

Asia WGS AF: 0.365 AC: 1274 AN: 3478

EpiCase AF: 0.503

EpiControl AF: 0.512

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

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

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	-0.41
CADD	Benign	19
DANN	Benign	0.91

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: rs1803893; hg19: chr3-39449137; COSMIC: COSV57191604; COSMIC: COSV57191604;