chr19-41864559-A-G

Variant names:

• chr19-41864559-A-G
• rs12974044
• NM_001022.4:c.172+3347A>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+3347A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,232 control chromosomes in the GnomAD database, including 6,085 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 0.26 (6080 hom., cov: 31)
  • Exomes 𝑓: 0.23 (5 hom.)
• Consequence: RPS19 NM_001022.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192
• Publications: 13 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.377 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+3347A>G		intron	N/A	NP_001013.1	B0ZBD0
	RPS19	NM_001321485.2		c.185+3334A>G		intron	N/A	NP_001308414.1
	RPS19	NM_001321483.2		c.172+3347A>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+3347A>G		intron	N/A	ENSP00000470972.1	P39019
	RPS19	ENST00000593863.5	TSL:3	c.172+3347A>G		intron	N/A	ENSP00000470004.1	P39019
	RPS19	ENST00000600467.6	TSL:2	c.172+3347A>G		intron	N/A	ENSP00000469228.2	P39019

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39040 AN: 151996 Hom.: 6081 Cov.: 31

Gnomad AFR AF: 0.0844

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.300

GnomAD4 exome AF: 0.229 AC: 27 AN: 118 Hom.: 5 Cov.: 0 AF XY: 0.262 AC XY: 22 AN XY: 84

African (AFR) AF: 0.00 AC: 0 AN: 6

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.228 AC: 21 AN: 92

Other (OTH) AF: 0.357 AC: 5 AN: 14

GnomAD4 genome AF: 0.257 AC: 39034 AN: 152114 Hom.: 6080 Cov.: 31 AF XY: 0.260 AC XY: 19358 AN XY: 74358

African (AFR) AF: 0.0842 AC: 3498 AN: 41542

American (AMR) AF: 0.344 AC: 5258 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1412 AN: 3464

East Asian (EAS) AF: 0.185 AC: 956 AN: 5168

South Asian (SAS) AF: 0.392 AC: 1886 AN: 4816

European-Finnish (FIN) AF: 0.291 AC: 3076 AN: 10572

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21847 AN: 67956

Other (OTH) AF: 0.296 AC: 626 AN: 2112

Alfa AF: 0.304 Hom.: 26792

Bravo AF: 0.249

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.79
PhyloP100		0.19

Splicing

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

Other links and lift over

dbSNP: rs12974044; hg19: chr19-42368629;