rs2075749

chr19-41860935-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001022.4(RPS19):c.71+90C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 1,301,316 control chromosomes in the GnomAD database, including 168,776 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 0.45 (16458 hom., cov: 33)
  • Exomes 𝑓: 0.51 (152318 hom.)
• Consequence: RPS19 NM_001022.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.739

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (Cadd=1.325).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS19	NM_001022.4	c.71+90C>G		intron_variant		ENST00000598742.6
RPS19	NM_001321483.2	c.71+90C>G		intron_variant
RPS19	NM_001321484.2	c.71+90C>G		intron_variant
RPS19	NM_001321485.2	c.71+90C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS19	ENST00000598742.6	c.71+90C>G		intron_variant		1	NM_001022.4	P1

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68665 AN: 151654 Hom.: 16446 Cov.: 33

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.503

GnomAD4 exome AF: 0.511 AC: 586860 AN: 1149546 Hom.: 152318 Cov.: 16 AF XY: 0.515 AC XY: 302136 AN XY: 586194

Gnomad4 AFR exome AF: 0.275

Gnomad4 AMR exome AF: 0.501

Gnomad4 ASJ exome AF: 0.655

Gnomad4 EAS exome AF: 0.464

Gnomad4 SAS exome AF: 0.592

Gnomad4 FIN exome AF: 0.520

Gnomad4 NFE exome AF: 0.507

Gnomad4 OTH exome AF: 0.516

GnomAD4 genome AF: 0.453 AC: 68711 AN: 151770 Hom.: 16458 Cov.: 33 AF XY: 0.457 AC XY: 33880 AN XY: 74118

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.505

Gnomad4 ASJ AF: 0.653

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.512

Gnomad4 NFE AF: 0.513

Gnomad4 OTH AF: 0.498

Alfa AF: 0.483 Hom.: 2265

Bravo AF: 0.442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Cadd	Benign	1.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2075749; hg19: -;