chr19-41863946-A-G

Position:

• chr19-41863946-A-G

Variant summary

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

The NM_001022.4(RPS19):​c.172+2734A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 150,616 control chromosomes in the GnomAD database, including 30,078 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 0.63 (30061 hom., cov: 25)
  • Exomes 𝑓: 0.66 (17 hom.)
• Consequence: RPS19 NM_001022.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.38

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 (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS19	NM_001022.4	c.172+2734A>G		intron_variant		ENST00000598742.6
RPS19	NM_001321483.2	c.172+2734A>G		intron_variant
RPS19	NM_001321484.2	c.172+2734A>G		intron_variant
RPS19	NM_001321485.2	c.185+2721A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS19	ENST00000598742.6	c.172+2734A>G		intron_variant		1	NM_001022.4	P1

Frequencies

GnomAD3 genomes AF: 0.628 AC: 94488 AN: 150424 Hom.: 30026 Cov.: 25

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.724

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.793

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.645

GnomAD4 exome AF: 0.662 AC: 49 AN: 74 Hom.: 17 Cov.: 0 AF XY: 0.655 AC XY: 38 AN XY: 58

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.655

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.628 AC: 94576 AN: 150542 Hom.: 30061 Cov.: 25 AF XY: 0.636 AC XY: 46653 AN XY: 73400

Gnomad4 AFR AF: 0.696

Gnomad4 AMR AF: 0.596

Gnomad4 ASJ AF: 0.724

Gnomad4 EAS AF: 0.709

Gnomad4 SAS AF: 0.793

Gnomad4 FIN AF: 0.622

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.646

Alfa AF: 0.598 Hom.: 3255

Bravo AF: 0.624

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12972552; hg19: chr19-42368016;