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GeneBe

19-1440172-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001018.5(RPS15):c.243G>A(p.Arg81=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000209 in 1,612,592 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

RPS15
NM_001018.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.12
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 -11 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=-0.66).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-1440172-G-A is Benign according to our data. Variant chr19-1440172-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3038588.Status of the report is criteria_provided_single_submitter, 1 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=-2.12 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd4 at 26 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPS15NM_001018.5 linkuse as main transcriptc.243G>A p.Arg81= synonymous_variant 3/4 ENST00000592588.7
RPS15NM_001308226.2 linkuse as main transcriptc.264G>A p.Arg88= synonymous_variant 3/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPS15ENST00000592588.7 linkuse as main transcriptc.243G>A p.Arg81= synonymous_variant 3/41 NM_001018.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000171
AC:
26
AN:
152256
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00259
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000220
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000244
AC:
60
AN:
245692
Hom.:
0
AF XY:
0.000241
AC XY:
32
AN XY:
132858
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000146
Gnomad ASJ exome
AF:
0.00227
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000333
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000235
Gnomad OTH exome
AF:
0.00102
GnomAD4 exome
AF:
0.000213
AC:
311
AN:
1460336
Hom.:
0
Cov.:
33
AF XY:
0.000222
AC XY:
161
AN XY:
726266
show subpopulations
Gnomad4 AFR exome
AF:
0.000179
Gnomad4 AMR exome
AF:
0.000202
Gnomad4 ASJ exome
AF:
0.00182
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000350
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000184
Gnomad4 OTH exome
AF:
0.000448
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000171
AC:
26
AN:
152256
Hom.:
0
Cov.:
33
AF XY:
0.000121
AC XY:
9
AN XY:
74382
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00259
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000220
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000278
Hom.:
0
Bravo
AF:
0.000234

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

RPS15-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesSep 27, 2023This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.66
CADD
Benign
0.27
DANN
Benign
0.84
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs367617949; hg19: chr19-1440171; COSMIC: COSV51834812; COSMIC: COSV51834812; API