19-41863834-C-T

Position:

• chr19-41863834-C-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347

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=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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS19	NM_001022.4	c.172+2622C>T		intron_variant		ENST00000598742.6	NP_001013.1
RPS19	NM_001321485.2	c.185+2609C>T		intron_variant			NP_001308414.1
RPS19	NM_001321483.2	c.172+2622C>T		intron_variant			NP_001308412.1
RPS19	NM_001321484.2	c.172+2622C>T		intron_variant			NP_001308413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS19	ENST00000598742.6	c.172+2622C>T		intron_variant		1	NM_001022.4	ENSP00000470972.1

Frequencies

GnomAD3 genomes AF: 0.458 AC: 67240 AN: 146804 Hom.: 16271 Cov.: 25

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: 19 AN: 48 Hom.: 7 Cov.: 0 AF XY: 0.395 AC XY: 15 AN XY: 38

Gnomad4 AFR exome AF: 0.00

Gnomad4 SAS exome AF: 0.667

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.467

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.458 AC: 67271 AN: 146858 Hom.: 16282 Cov.: 25 AF XY: 0.462 AC XY: 32770 AN XY: 70918

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.571

Gnomad4 FIN AF: 0.520

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.505

Alfa AF: 0.472 Hom.: 2535

Bravo AF: 0.446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	2.4

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs873282; hg19: -;