Genetic Variant RPS19:c.172+2622C>T (chr19-41863834-C-T) – 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+2622C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 146,906 control chromosomes in the GnomAD database, including 16,289 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 0.46 ( 16282 hom., cov: 25)

Exomes 𝑓: 0.40 ( 7 hom. )

Consequence

RPS19
NM_001022.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.347

Publications

4 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=2.356).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RPS19	NM_001022.4 link	c.172+2622C>T	intron_variant	Intron 3 of 5	ENST00000598742.6	NP_001013.1	P39019B0ZBD0
RPS19	NM_001321485.2 link	c.185+2609C>T	intron_variant	Intron 3 of 5		NP_001308414.1
RPS19	NM_001321483.2 link	c.172+2622C>T	intron_variant	Intron 3 of 5		NP_001308412.1	P39019B0ZBD0
RPS19	NM_001321484.2 link	c.172+2622C>T	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+2622C>T		intron_variant	Intron 3 of 5	1	NM_001022.4	ENSP00000470972.1		P39019

Frequencies

GnomAD3 genomes

AF:

0.458

AC:

67240

AN:

146804

Hom.:

16271

Cov.:

show subpopulations

Gnomad AFR

AF:

0.293

Gnomad AMI

AF:

0.563

Gnomad AMR

AF:

0.504

Gnomad ASJ

AF:

0.655

Gnomad EAS

AF:

0.457

Gnomad SAS

AF:

0.572

Gnomad FIN

AF:

0.520

Gnomad MID

AF:

0.699

Gnomad NFE

AF:

0.515

Gnomad OTH

AF:

0.508

GnomAD4 exome

AF:

0.396

AC:

AN:

Hom.:

Cov.:

AF XY:

0.395

AC XY:

AN XY:

show subpopulations

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:

0.667

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.467

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.458

AC:

67271

AN:

146858

Hom.:

16282

Cov.:

AF XY:

0.462

AC XY:

32770

AN XY:

70918

show subpopulations

African (AFR)

AF:

0.294

AC:

11671

AN:

39742

American (AMR)

AF:

0.504

AC:

7343

AN:

14560

Ashkenazi Jewish (ASJ)

AF:

0.655

AC:

2263

AN:

3456

East Asian (EAS)

AF:

0.458

AC:

2267

AN:

4954

South Asian (SAS)

AF:

0.571

AC:

2683

AN:

4696

European-Finnish (FIN)

AF:

0.520

AC:

4622

AN:

8890

Middle Eastern (MID)

AF:

0.700

AC:

196

AN:

280

European-Non Finnish (NFE)

AF:

0.515

AC:

34685

AN:

67332

Other (OTH)

AF:

0.505

AC:

1031

AN:

2042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1662

3324

4986

6648

8310

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

628

1256

1884

2512

3140

<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:

0.466

Hom.:

2567

Bravo

AF:

0.446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

CADD

Benign

2.4

(source)

PhyloP100

0.35

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