19-41863834-C-T

Variant names:

• chr19-41863834-C-T
• rs873282
• NM_001022.4:c.172+2622C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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: Orphanet, ClinGen
• Diamond-Blackfan anemia 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001022.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS19	NM_001022.4	MANE Select	c.172+2622C>T		intron	N/A	NP_001013.1	B0ZBD0
	RPS19	NM_001321485.2		c.185+2609C>T		intron	N/A	NP_001308414.1
	RPS19	NM_001321483.2		c.172+2622C>T		intron	N/A	NP_001308412.1	B0ZBD0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS19	ENST00000598742.6	TSL:1 MANE Select	c.172+2622C>T		intron	N/A	ENSP00000470972.1	P39019
	RPS19	ENST00000593863.5	TSL:3	c.172+2622C>T		intron	N/A	ENSP00000470004.1	P39019
	RPS19	ENST00000600467.6	TSL:2	c.172+2622C>T		intron	N/A	ENSP00000469228.2	P39019

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

African (AFR) AF: 0.00 AC: 0 AN: 8

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.667 AC: 4 AN: 6

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.467 AC: 14 AN: 30

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.294 AC: 11671 AN: 39742

American (AMR) AF: 0.504 AC: 7343 AN: 14560

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 2263 AN: 3456

East Asian (EAS) AF: 0.458 AC: 2267 AN: 4954

South Asian (SAS) AF: 0.571 AC: 2683 AN: 4696

European-Finnish (FIN) AF: 0.520 AC: 4622 AN: 8890

Middle Eastern (MID) AF: 0.700 AC: 196 AN: 280

European-Non Finnish (NFE) AF: 0.515 AC: 34685 AN: 67332

Other (OTH) AF: 0.505 AC: 1031 AN: 2042

Alfa AF: 0.466 Hom.: 2567

Bravo AF: 0.446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
CADD	Benign	2.4
PhyloP100		0.35

Splicing

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

Other links and lift over

dbSNP: rs873282;