chr19-41864012-T-G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001022.4(RPS19):​c.172+2800T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00487 in 152,050 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0049 ( 4 hom., cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

RPS19
NM_001022.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.79

Publications

1 publications found
Variant links:
Genes affected
RPS19 (HGNC:10402): (ribosomal protein S19) 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 S19E family of ribosomal proteins. It is located in the cytoplasm. Mutations in this gene cause Diamond-Blackfan anemia (DBA), a constitutional erythroblastopenia characterized by absent or decreased erythroid precursors, in a subset of patients. This suggests a possible extra-ribosomal function for this gene in erythropoietic differentiation and proliferation, in addition to its ribosomal function. Higher expression levels of this gene in some primary colon carcinomas compared to matched normal colon tissues has been observed. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]
RPS19 Gene-Disease associations (from GenCC):
  • Diamond-Blackfan anemia
    Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
  • Diamond-Blackfan anemia 1
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BS2
High AC in GnomAd4 at 740 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RPS19NM_001022.4 linkc.172+2800T>G intron_variant Intron 3 of 5 ENST00000598742.6 NP_001013.1 P39019B0ZBD0
RPS19NM_001321485.2 linkc.185+2787T>G intron_variant Intron 3 of 5 NP_001308414.1
RPS19NM_001321483.2 linkc.172+2800T>G intron_variant Intron 3 of 5 NP_001308412.1 P39019B0ZBD0
RPS19NM_001321484.2 linkc.172+2800T>G intron_variant Intron 3 of 5 NP_001308413.1 P39019B0ZBD0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RPS19ENST00000598742.6 linkc.172+2800T>G intron_variant Intron 3 of 5 1 NM_001022.4 ENSP00000470972.1 P39019

Frequencies

GnomAD3 genomes
AF:
0.00488
AC:
741
AN:
151932
Hom.:
4
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00164
Gnomad AMI
AF:
0.0384
Gnomad AMR
AF:
0.00826
Gnomad ASJ
AF:
0.00288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000623
Gnomad FIN
AF:
0.000473
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00706
Gnomad OTH
AF:
0.00624
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
72
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
50
African (AFR)
AC:
0
AN:
0
American (AMR)
AF:
0.00
AC:
0
AN:
2
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
2
East Asian (EAS)
AC:
0
AN:
0
South Asian (SAS)
AF:
0.00
AC:
0
AN:
10
European-Finnish (FIN)
AC:
0
AN:
0
Middle Eastern (MID)
AC:
0
AN:
0
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
50
Other (OTH)
AF:
0.00
AC:
0
AN:
8
GnomAD4 genome
AF:
0.00487
AC:
740
AN:
152050
Hom.:
4
Cov.:
31
AF XY:
0.00478
AC XY:
355
AN XY:
74324
show subpopulations
African (AFR)
AF:
0.00164
AC:
68
AN:
41460
American (AMR)
AF:
0.00825
AC:
126
AN:
15274
Ashkenazi Jewish (ASJ)
AF:
0.00288
AC:
10
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5172
South Asian (SAS)
AF:
0.000624
AC:
3
AN:
4810
European-Finnish (FIN)
AF:
0.000473
AC:
5
AN:
10580
Middle Eastern (MID)
AF:
0.00340
AC:
1
AN:
294
European-Non Finnish (NFE)
AF:
0.00705
AC:
479
AN:
67976
Other (OTH)
AF:
0.00618
AC:
13
AN:
2104
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
38
76
113
151
189
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
10
20
30
40
50
<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:
0.0000702
Hom.:
0
Bravo
AF:
0.00584

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
1.6
DANN
Benign
0.21
PhyloP100
-1.8

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs61761234; hg19: chr19-42368082; API