19-41863946-A-G

Variant names:

• chr19-41863946-A-G
• rs12972552
• NM_001022.4:c.172+2734A>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.172+2734A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 150,616 control chromosomes in the GnomAD database, including 30,078 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 0.63 (30061 hom., cov: 25)
  • Exomes 𝑓: 0.66 (17 hom.)
• Consequence: RPS19 NM_001022.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.38
• 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 (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.772 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+2734A>G		intron	N/A	NP_001013.1	B0ZBD0
	RPS19	NM_001321485.2		c.185+2721A>G		intron	N/A	NP_001308414.1
	RPS19	NM_001321483.2		c.172+2734A>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.172+2734A>G		intron	N/A	ENSP00000470972.1	P39019
	RPS19	ENST00000593863.5	TSL:3	c.172+2734A>G		intron	N/A	ENSP00000470004.1	P39019
	RPS19	ENST00000600467.6	TSL:2	c.172+2734A>G		intron	N/A	ENSP00000469228.2	P39019

Frequencies

GnomAD3 genomes AF: 0.628 AC: 94488 AN: 150424 Hom.: 30026 Cov.: 25

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.724

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.793

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.645

GnomAD4 exome AF: 0.662 AC: 49 AN: 74 Hom.: 17 Cov.: 0 AF XY: 0.655 AC XY: 38 AN XY: 58

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.655 AC: 38 AN: 58

Other (OTH) AF: 0.750 AC: 3 AN: 4

GnomAD4 genome AF: 0.628 AC: 94576 AN: 150542 Hom.: 30061 Cov.: 25 AF XY: 0.636 AC XY: 46653 AN XY: 73400

African (AFR) AF: 0.696 AC: 28389 AN: 40810

American (AMR) AF: 0.596 AC: 8977 AN: 15074

Ashkenazi Jewish (ASJ) AF: 0.724 AC: 2503 AN: 3456

East Asian (EAS) AF: 0.709 AC: 3606 AN: 5086

South Asian (SAS) AF: 0.793 AC: 3784 AN: 4774

European-Finnish (FIN) AF: 0.622 AC: 6419 AN: 10318

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.571 AC: 38691 AN: 67740

Other (OTH) AF: 0.646 AC: 1347 AN: 2084

Alfa AF: 0.598 Hom.: 3255

Bravo AF: 0.624

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.65
PhyloP100		-3.4

Splicing

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

Other links and lift over

dbSNP: rs12972552; hg19: chr19-42368016;