19-41870766-G-T

Variant names:

• chr19-41870766-G-T
• rs2075752
• NM_001022.4:c.412-585G>T

Variant summary

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

The NM_001022.4(RPS19):​c.412-585G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 150,480 control chromosomes in the GnomAD database, including 15,044 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 0.42 (15044 hom., cov: 27)
• Consequence: RPS19 NM_001022.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.294
• 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: 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS19	NM_001022.4	c.412-585G>T		intron_variant	Intron 5 of 5	ENST00000598742.6	NP_001013.1
RPS19	NM_001321485.2	c.425-585G>T		intron_variant	Intron 5 of 5		NP_001308414.1
RPS19	NM_001321483.2	c.412-585G>T		intron_variant	Intron 5 of 5		NP_001308412.1
RPS19	NM_001321484.2	c.412-585G>T		intron_variant	Intron 5 of 5		NP_001308413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS19	ENST00000598742.6	c.412-585G>T		intron_variant	Intron 5 of 5	1	NM_001022.4	ENSP00000470972.1
RPS19	ENST00000593863.5	c.412-585G>T		intron_variant	Intron 5 of 5	3		ENSP00000470004.1
RPS19	ENST00000600467.6	c.412-585G>T		intron_variant	Intron 5 of 5	2		ENSP00000469228.2
RPS19	ENST00000221975.6	c.190-585G>T		intron_variant	Intron 5 of 5	3		ENSP00000221975.2

Frequencies

GnomAD3 genomes AF: 0.416 AC: 62492 AN: 150376 Hom.: 15046 Cov.: 27

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.472

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

GnomAD4 genome AF: 0.415 AC: 62489 AN: 150480 Hom.: 15044 Cov.: 27 AF XY: 0.420 AC XY: 30849 AN XY: 73368

African (AFR) AF: 0.152 AC: 6205 AN: 40910

American (AMR) AF: 0.490 AC: 7365 AN: 15038

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2124 AN: 3462

East Asian (EAS) AF: 0.459 AC: 2330 AN: 5076

South Asian (SAS) AF: 0.572 AC: 2737 AN: 4784

European-Finnish (FIN) AF: 0.519 AC: 5283 AN: 10180

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34759 AN: 67750

Other (OTH) AF: 0.468 AC: 973 AN: 2078

Alfa AF: 0.467 Hom.: 7423

Bravo AF: 0.398

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.81
PhyloP100		0.29

Splicing

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

Other links and lift over

dbSNP: rs2075752; hg19: chr19-42374836;