19-41860935-C-G

Variant names:

• chr19-41860935-C-G
• rs2075749
• NM_001022.4:c.71+90C>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.71+90C>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 1,301,316 control chromosomes in the GnomAD database, including 168,776 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 0.45 (16458 hom., cov: 33)
  • Exomes 𝑓: 0.51 (152318 hom.)
• Consequence: RPS19 NM_001022.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.739
• Publications: 7 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=1.325).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.554 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.71+90C>G		intron	N/A	NP_001013.1	B0ZBD0
	RPS19	NM_001321485.2		c.71+90C>G		intron	N/A	NP_001308414.1
	RPS19	NM_001321483.2		c.71+90C>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.71+90C>G		intron	N/A	ENSP00000470972.1	P39019
	RPS19	ENST00000593863.5	TSL:3	c.71+90C>G		intron	N/A	ENSP00000470004.1	P39019
	RPS19	ENST00000600467.6	TSL:2	c.71+90C>G		intron	N/A	ENSP00000469228.2	P39019

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68665 AN: 151654 Hom.: 16446 Cov.: 33

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.503

GnomAD4 exome AF: 0.511 AC: 586860 AN: 1149546 Hom.: 152318 Cov.: 16 AF XY: 0.515 AC XY: 302136 AN XY: 586194

African (AFR) AF: 0.275 AC: 7492 AN: 27274

American (AMR) AF: 0.501 AC: 21985 AN: 43850

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 15898 AN: 24282

East Asian (EAS) AF: 0.464 AC: 17708 AN: 38174

South Asian (SAS) AF: 0.592 AC: 47298 AN: 79952

European-Finnish (FIN) AF: 0.520 AC: 27550 AN: 52932

Middle Eastern (MID) AF: 0.684 AC: 2438 AN: 3564

European-Non Finnish (NFE) AF: 0.507 AC: 420769 AN: 829698

Other (OTH) AF: 0.516 AC: 25722 AN: 49820

GnomAD4 genome AF: 0.453 AC: 68711 AN: 151770 Hom.: 16458 Cov.: 33 AF XY: 0.457 AC XY: 33880 AN XY: 74118

African (AFR) AF: 0.282 AC: 11682 AN: 41442

American (AMR) AF: 0.505 AC: 7709 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2262 AN: 3464

East Asian (EAS) AF: 0.459 AC: 2364 AN: 5152

South Asian (SAS) AF: 0.572 AC: 2754 AN: 4812

European-Finnish (FIN) AF: 0.512 AC: 5357 AN: 10462

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

European-Non Finnish (NFE) AF: 0.513 AC: 34824 AN: 67876

Other (OTH) AF: 0.498 AC: 1049 AN: 2106

Alfa AF: 0.483 Hom.: 2265

Bravo AF: 0.442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
CADD	Benign	1.3
PhyloP100		-0.74
PromoterAI		-0.024	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2075749;