dbSNP rs61761232: RPS19:c.172+2623G>A (chr19-41863835-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001022.4(RPS19):c.172+2623G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00262 in 146,048 control chromosomes in the GnomAD database, including 6 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 0.0026 ( 6 hom., cov: 28)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RPS19
NM_001022.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.04

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

RPS19 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (Cadd=0.35).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RPS19	NM_001022.4 link	c.172+2623G>A	intron_variant	Intron 3 of 5	ENST00000598742.6	NP_001013.1	P39019B0ZBD0
RPS19	NM_001321485.2 link	c.185+2610G>A	intron_variant	Intron 3 of 5		NP_001308414.1
RPS19	NM_001321483.2 link	c.172+2623G>A	intron_variant	Intron 3 of 5		NP_001308412.1	P39019B0ZBD0
RPS19	NM_001321484.2 link	c.172+2623G>A	intron_variant	Intron 3 of 5		NP_001308413.1	P39019B0ZBD0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS19	ENST00000598742.6 link	c.172+2623G>A		intron_variant	Intron 3 of 5	1	NM_001022.4	ENSP00000470972.1		P39019

Frequencies

GnomAD3 genomes

AF:

0.00265

AC:

387

AN:

145976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000857

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000404

Gnomad SAS

AF:

0.0602

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00974

Gnomad NFE

AF:

0.00126

Gnomad OTH

AF:

0.00353

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.00262

AC:

382

AN:

146048

Hom.:

Cov.:

AF XY:

0.00352

AC XY:

249

AN XY:

70702

show subpopulations

African (AFR)

AF:

0.000173

AC:

AN:

40442

American (AMR)

AF:

0.000856

AC:

AN:

14022

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3406

East Asian (EAS)

AF:

0.000405

AC:

AN:

4942

South Asian (SAS)

AF:

0.0594

AC:

268

AN:

4508

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8896

Middle Eastern (MID)

AF:

0.0106

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.00126

AC:

AN:

66652

Other (OTH)

AF:

0.00299

AC:

AN:

2004

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00153

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

CADD

Benign

0.35

(source)

PhyloP100

-2.0

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over