rs2075754

Variant names:

• chr19-41871176-T-C
• rs2075754
• NM_001022.4:c.412-175T>C

Variant summary

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

The NM_001022.4(RPS19):​c.412-175T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 151,462 control chromosomes in the GnomAD database, including 16,657 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 (16657 hom., cov: 29)
• Consequence: RPS19 NM_001022.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.511
• Publications: 12 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 (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS19	NM_001022.4	c.412-175T>C		intron_variant	Intron 5 of 5	ENST00000598742.6	NP_001013.1
RPS19	NM_001321485.2	c.425-175T>C		intron_variant	Intron 5 of 5		NP_001308414.1
RPS19	NM_001321483.2	c.412-175T>C		intron_variant	Intron 5 of 5		NP_001308412.1
RPS19	NM_001321484.2	c.412-175T>C		intron_variant	Intron 5 of 5		NP_001308413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS19	ENST00000598742.6	c.412-175T>C		intron_variant	Intron 5 of 5	1	NM_001022.4	ENSP00000470972.1
RPS19	ENST00000593863.5	c.412-175T>C		intron_variant	Intron 5 of 5	3		ENSP00000470004.1
RPS19	ENST00000600467.6	c.412-175T>C		intron_variant	Intron 5 of 5	2		ENSP00000469228.2
RPS19	ENST00000221975.6	c.190-175T>C		intron_variant	Intron 5 of 5	3		ENSP00000221975.2

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69066 AN: 151344 Hom.: 16642 Cov.: 29

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.691

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.508

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

GnomAD4 genome AF: 0.456 AC: 69119 AN: 151462 Hom.: 16657 Cov.: 29 AF XY: 0.461 AC XY: 34117 AN XY: 74018

African (AFR) AF: 0.290 AC: 11969 AN: 41224

American (AMR) AF: 0.507 AC: 7716 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2268 AN: 3468

East Asian (EAS) AF: 0.458 AC: 2342 AN: 5116

South Asian (SAS) AF: 0.574 AC: 2753 AN: 4796

European-Finnish (FIN) AF: 0.517 AC: 5429 AN: 10510

Middle Eastern (MID) AF: 0.692 AC: 202 AN: 292

European-Non Finnish (NFE) AF: 0.514 AC: 34871 AN: 67822

Other (OTH) AF: 0.502 AC: 1055 AN: 2100

Alfa AF: 0.510 Hom.: 16378

Bravo AF: 0.444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.2
PhyloP100		-0.51

Splicing

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

Other links and lift over

dbSNP: rs2075754; hg19: chr19-42375244;