rs61762296

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000598742.6(RPS19):c.411+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00441 in 1,613,908 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0046 ( 46 hom. )

Consequence

RPS19
ENST00000598742.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.0200

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 19-41869765-G-A is Benign according to our data. Variant chr19-41869765-G-A is described in ClinVar as [Benign]. Clinvar id is 212065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00301 (458/152314) while in subpopulation SAS AF= 0.00664 (32/4822). AF 95% confidence interval is 0.00483. There are 1 homozygotes in gnomad4. There are 238 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 458 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
RPS19	NM_001022.4 linkuse as main transcript	c.411+12G>A	intron_variant	ENST00000598742.6	NP_001013.1
RPS19	NM_001321483.2 linkuse as main transcript	c.411+12G>A	intron_variant		NP_001308412.1
RPS19	NM_001321484.2 linkuse as main transcript	c.411+12G>A	intron_variant		NP_001308413.1
RPS19	NM_001321485.2 linkuse as main transcript	c.424+12G>A	intron_variant		NP_001308414.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
RPS19	ENST00000598742.6 linkuse as main transcript	c.411+12G>A	intron_variant	1	NM_001022.4	ENSP00000470972	P1
RPS19	ENST00000221975.6 linkuse as main transcript	c.189+12G>A	intron_variant	3		ENSP00000221975
RPS19	ENST00000593863.5 linkuse as main transcript	c.411+12G>A	intron_variant	3		ENSP00000470004	P1
RPS19	ENST00000600467.6 linkuse as main transcript	c.411+12G>A	intron_variant	2		ENSP00000469228	P1

Frequencies

GnomAD3 genomes

AF:

0.00301

AC:

458

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00684

Gnomad FIN

AF:

0.00603

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00386

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00482

AC:

1210

AN:

251086

Hom.:

AF XY:

0.00512

AC XY:

695

AN XY:

135742

show subpopulations

Gnomad AFR exome

AF:

0.000494

Gnomad AMR exome

AF:

0.00191

Gnomad ASJ exome

AF:

0.00487

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00973

Gnomad FIN exome

AF:

0.00754

Gnomad NFE exome

AF:

0.00517

Gnomad OTH exome

AF:

0.00636

GnomAD4 exome

AF:

0.00455

AC:

6654

AN:

1461594

Hom.:

Cov.:

AF XY:

0.00475

AC XY:

3457

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.00170

Gnomad4 ASJ exome

AF:

0.00497

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0104

Gnomad4 FIN exome

AF:

0.00841

Gnomad4 NFE exome

AF:

0.00427

Gnomad4 OTH exome

AF:

0.00512

GnomAD4 genome

AF:

0.00301

AC:

458

AN:

152314

Hom.:

Cov.:

AF XY:

0.00320

AC XY:

238

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.00320

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00664

Gnomad4 FIN

AF:

0.00603

Gnomad4 NFE

AF:

0.00388

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00277

Hom.:

Bravo

AF:

0.00260

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2023	RPS19: BS1, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 26, 2018

- -

Diamond-Blackfan anemia 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Diamond-Blackfan anemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.21

DANN

Benign

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over