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19-1438866-C-T

Variant summary

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

The NM_001018.5(RPS15):c.63C>T(p.Asp21=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0519 in 1,590,574 control chromosomes in the GnomAD database, including 2,450 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.054 ( 258 hom., cov: 32)
Exomes 𝑓: 0.052 ( 2192 hom. )

Consequence

RPS15
NM_001018.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.251
Variant links:
Genes affected
RPS15 (HGNC:10388): (ribosomal protein S15) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S19P family of ribosomal proteins. It is located in the cytoplasm. This gene has been found to be activated in various tumors, such as insulinomas, esophageal cancers, and colon cancers. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-1438866-C-T is Benign according to our data. Variant chr19-1438866-C-T is described in ClinVar as [Benign]. Clinvar id is 440243.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.251 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0633 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPS15NM_001018.5 linkuse as main transcriptc.63C>T p.Asp21= synonymous_variant 2/4 ENST00000592588.7
RPS15NM_001308226.2 linkuse as main transcriptc.84C>T p.Asp28= synonymous_variant 2/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPS15ENST00000592588.7 linkuse as main transcriptc.63C>T p.Asp21= synonymous_variant 2/41 NM_001018.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0538
AC:
8190
AN:
152170
Hom.:
254
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0483
Gnomad AMI
AF:
0.0417
Gnomad AMR
AF:
0.0428
Gnomad ASJ
AF:
0.0853
Gnomad EAS
AF:
0.0358
Gnomad SAS
AF:
0.0704
Gnomad FIN
AF:
0.0782
Gnomad MID
AF:
0.0823
Gnomad NFE
AF:
0.0539
Gnomad OTH
AF:
0.0735
GnomAD3 exomes
AF:
0.0526
AC:
11189
AN:
212584
Hom.:
346
AF XY:
0.0551
AC XY:
6362
AN XY:
115492
show subpopulations
Gnomad AFR exome
AF:
0.0464
Gnomad AMR exome
AF:
0.0230
Gnomad ASJ exome
AF:
0.0837
Gnomad EAS exome
AF:
0.0387
Gnomad SAS exome
AF:
0.0776
Gnomad FIN exome
AF:
0.0779
Gnomad NFE exome
AF:
0.0510
Gnomad OTH exome
AF:
0.0470
GnomAD4 exome
AF:
0.0517
AC:
74306
AN:
1438288
Hom.:
2192
Cov.:
32
AF XY:
0.0530
AC XY:
37822
AN XY:
713588
show subpopulations
Gnomad4 AFR exome
AF:
0.0455
Gnomad4 AMR exome
AF:
0.0246
Gnomad4 ASJ exome
AF:
0.0848
Gnomad4 EAS exome
AF:
0.0287
Gnomad4 SAS exome
AF:
0.0767
Gnomad4 FIN exome
AF:
0.0752
Gnomad4 NFE exome
AF:
0.0497
Gnomad4 OTH exome
AF:
0.0539
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0539
AC:
8212
AN:
152286
Hom.:
258
Cov.:
32
AF XY:
0.0558
AC XY:
4152
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.0487
Gnomad4 AMR
AF:
0.0427
Gnomad4 ASJ
AF:
0.0853
Gnomad4 EAS
AF:
0.0357
Gnomad4 SAS
AF:
0.0694
Gnomad4 FIN
AF:
0.0782
Gnomad4 NFE
AF:
0.0539
Gnomad4 OTH
AF:
0.0761
Alfa
AF:
0.0530
Hom.:
158
Bravo
AF:
0.0495
Asia WGS
AF:
0.0820
AC:
284
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesFeb 07, 2017- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMay 04, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.46
CADD
Benign
12
DANN
Benign
0.97
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.9

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.

Other links and lift over

dbSNP: rs7251165; hg19: chr19-1438865; COSMIC: COSV51833007; COSMIC: COSV51833007; API