19-41862159-A-G

Variant names:

• chr19-41862159-A-G
• rs3786539
• NM_001022.4:c.172+947A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001022.4(RPS19):​c.172+947A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 151,832 control chromosomes in the GnomAD database, including 6,052 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 0.26 (6052 hom., cov: 32)
• Consequence: RPS19 NM_001022.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199
• Publications: 6 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (Cadd=4.673).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS19	NM_001022.4	c.172+947A>G		intron_variant	Intron 3 of 5	ENST00000598742.6	NP_001013.1
RPS19	NM_001321485.2	c.185+934A>G		intron_variant	Intron 3 of 5		NP_001308414.1
RPS19	NM_001321483.2	c.172+947A>G		intron_variant	Intron 3 of 5		NP_001308412.1
RPS19	NM_001321484.2	c.172+947A>G		intron_variant	Intron 3 of 5		NP_001308413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS19	ENST00000598742.6	c.172+947A>G		intron_variant	Intron 3 of 5	1	NM_001022.4	ENSP00000470972.1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 38967 AN: 151714 Hom.: 6053 Cov.: 32

Gnomad AFR AF: 0.0849

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.300

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.257 AC: 38961 AN: 151832 Hom.: 6052 Cov.: 32 AF XY: 0.260 AC XY: 19302 AN XY: 74164

African (AFR) AF: 0.0847 AC: 3506 AN: 41382

American (AMR) AF: 0.344 AC: 5253 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1411 AN: 3468

East Asian (EAS) AF: 0.187 AC: 962 AN: 5150

South Asian (SAS) AF: 0.392 AC: 1888 AN: 4816

European-Finnish (FIN) AF: 0.285 AC: 2995 AN: 10518

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21846 AN: 67936

Other (OTH) AF: 0.297 AC: 623 AN: 2098

Alfa AF: 0.305 Hom.: 5649

Bravo AF: 0.249

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	4.7
PhyloP100		-0.20

Splicing

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

Other links and lift over

dbSNP: rs3786539; hg19: -;