chr19-41869228-A-G

Variant names:

• chr19-41869228-A-G
• rs1366610
• NM_001022.4:c.356+14A>G

Variant summary

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

The NM_001022.4(RPS19):​c.356+14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 1,610,130 control chromosomes in the GnomAD database, including 207,264 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 (16686 hom., cov: 31)
  • Exomes 𝑓: 0.51 (190578 hom.)
• Consequence: RPS19 NM_001022.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0590
• Publications: 11 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 (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.556 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.356+14A>G		intron	N/A	NP_001013.1	B0ZBD0
	RPS19	NM_001321485.2		c.369+14A>G		intron	N/A	NP_001308414.1
	RPS19	NM_001321483.2		c.356+14A>G		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.356+14A>G		intron	N/A	ENSP00000470972.1	P39019
	RPS19	ENST00000593863.5	TSL:3	c.356+14A>G		intron	N/A	ENSP00000470004.1	P39019
	RPS19	ENST00000600467.6	TSL:2	c.356+14A>G		intron	N/A	ENSP00000469228.2	P39019

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69198 AN: 151820 Hom.: 16671 Cov.: 31

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.507

GnomAD4 exome AF: 0.508 AC: 741459 AN: 1458192 Hom.: 190578 Cov.: 33 AF XY: 0.513 AC XY: 371913 AN XY: 725440

African (AFR) AF: 0.280 AC: 9363 AN: 33410

American (AMR) AF: 0.502 AC: 22357 AN: 44550

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 17135 AN: 26122

East Asian (EAS) AF: 0.464 AC: 18382 AN: 39636

South Asian (SAS) AF: 0.591 AC: 50832 AN: 86080

European-Finnish (FIN) AF: 0.520 AC: 27761 AN: 53340

Middle Eastern (MID) AF: 0.698 AC: 3456 AN: 4948

European-Non Finnish (NFE) AF: 0.506 AC: 561171 AN: 1109908

Other (OTH) AF: 0.515 AC: 31002 AN: 60198

GnomAD4 genome AF: 0.456 AC: 69250 AN: 151938 Hom.: 16686 Cov.: 31 AF XY: 0.460 AC XY: 34185 AN XY: 74238

African (AFR) AF: 0.290 AC: 12005 AN: 41440

American (AMR) AF: 0.506 AC: 7716 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2270 AN: 3470

East Asian (EAS) AF: 0.459 AC: 2359 AN: 5142

South Asian (SAS) AF: 0.574 AC: 2764 AN: 4818

European-Finnish (FIN) AF: 0.515 AC: 5446 AN: 10576

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.514 AC: 34916 AN: 67924

Other (OTH) AF: 0.502 AC: 1057 AN: 2106

Alfa AF: 0.449 Hom.: 2556

Bravo AF: 0.444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.1
PhyloP100		0.059

Splicing

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

Other links and lift over

dbSNP: rs1366610; hg19: chr19-42373298;