rs7250787

Variant names:

• chr19-41863549-A-T
• rs7250787
• NM_001022.4:c.172+2337A>T

Variant summary

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

The NM_001321485.2(RPS19):​c.185+2324A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 152,010 control chromosomes in the GnomAD database, including 16,760 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 (16760 hom., cov: 32)
• Consequence: RPS19 NM_001321485.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 2 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: ClinGen, Orphanet
• Diamond-Blackfan anemia 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, 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_001321485.2. 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+2337A>T		intron	N/A	NP_001013.1
	RPS19	NM_001321485.2		c.185+2324A>T		intron	N/A	NP_001308414.1
	RPS19	NM_001321483.2		c.172+2337A>T		intron	N/A	NP_001308412.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS19	ENST00000598742.6	TSL:1 MANE Select	c.172+2337A>T		intron	N/A	ENSP00000470972.1
	RPS19	ENST00000593863.5	TSL:3	c.172+2337A>T		intron	N/A	ENSP00000470004.1
	RPS19	ENST00000600467.6	TSL:2	c.172+2337A>T		intron	N/A	ENSP00000469228.2

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69478 AN: 151892 Hom.: 16743 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.509

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.457 AC: 69535 AN: 152010 Hom.: 16760 Cov.: 32 AF XY: 0.462 AC XY: 34347 AN XY: 74302

African (AFR) AF: 0.296 AC: 12262 AN: 41464

American (AMR) AF: 0.507 AC: 7737 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2270 AN: 3472

East Asian (EAS) AF: 0.458 AC: 2369 AN: 5170

South Asian (SAS) AF: 0.574 AC: 2769 AN: 4828

European-Finnish (FIN) AF: 0.516 AC: 5454 AN: 10560

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

European-Non Finnish (NFE) AF: 0.514 AC: 34896 AN: 67940

Other (OTH) AF: 0.503 AC: 1061 AN: 2108

Alfa AF: 0.484 Hom.: 2271

Bravo AF: 0.446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.16
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs7250787; hg19: chr19-42367621;