19-41869823-T-C

Position:

• chr19-41869823-T-C

Variant summary

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

The NM_001022.4(RPS19):​c.411+70T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,520,068 control chromosomes in the GnomAD database, including 77,521 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 (6075 hom., cov: 32)
  • Exomes 𝑓: 0.32 (71446 hom.)
• Consequence: RPS19 NM_001022.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.337

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS19	NM_001022.4	c.411+70T>C		intron_variant		ENST00000598742.6	NP_001013.1
RPS19	NM_001321485.2	c.424+70T>C		intron_variant			NP_001308414.1
RPS19	NM_001321483.2	c.411+70T>C		intron_variant			NP_001308412.1
RPS19	NM_001321484.2	c.411+70T>C		intron_variant			NP_001308413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS19	ENST00000598742.6	c.411+70T>C		intron_variant		1	NM_001022.4	ENSP00000470972.1
RPS19	ENST00000593863.5	c.411+70T>C		intron_variant		3		ENSP00000470004.1
RPS19	ENST00000600467.6	c.411+70T>C		intron_variant		2		ENSP00000469228.2
RPS19	ENST00000221975.6	c.189+70T>C		intron_variant		3		ENSP00000221975.2

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39070 AN: 152084 Hom.: 6076 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: 0.184

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.299

GnomAD4 exome AF: 0.318 AC: 435238 AN: 1367866 Hom.: 71446 AF XY: 0.322 AC XY: 220967 AN XY: 685384

Gnomad4 AFR exome AF: 0.0779

Gnomad4 AMR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.407

Gnomad4 EAS exome AF: 0.195

Gnomad4 SAS exome AF: 0.409

Gnomad4 FIN exome AF: 0.287

Gnomad4 NFE exome AF: 0.319

Gnomad4 OTH exome AF: 0.308

GnomAD4 genome AF: 0.257 AC: 39064 AN: 152202 Hom.: 6075 Cov.: 32 AF XY: 0.261 AC XY: 19385 AN XY: 74408

Gnomad4 AFR AF: 0.0846

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.296

Alfa AF: 0.315 Hom.: 4874

Bravo AF: 0.249

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2075751; hg19: chr19-42373893;