rs3786536

Variant names:

• chr19-41868387-A-C
• rs3786536
• NM_001022.4:c.173-644A>C

Your query was ambiguous. Multiple possible variants found:

• chr19-41868387-A-C
• chr19-41868387-A-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.173-644A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 152,052 control chromosomes in the GnomAD database, including 16,693 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 (16693 hom., cov: 32)
• Consequence: RPS19 NM_001022.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS19	NM_001022.4	c.173-644A>C		intron_variant	Intron 3 of 5	ENST00000598742.6	NP_001013.1
RPS19	NM_001321485.2	c.186-644A>C		intron_variant	Intron 3 of 5		NP_001308414.1
RPS19	NM_001321483.2	c.173-644A>C		intron_variant	Intron 3 of 5		NP_001308412.1
RPS19	NM_001321484.2	c.173-644A>C		intron_variant	Intron 3 of 5		NP_001308413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS19	ENST00000598742.6	c.173-644A>C		intron_variant	Intron 3 of 5	1	NM_001022.4	ENSP00000470972.1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69249 AN: 151934 Hom.: 16678 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.567

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: 0.507

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

GnomAD4 genome AF: 0.456 AC: 69301 AN: 152052 Hom.: 16693 Cov.: 32 AF XY: 0.461 AC XY: 34229 AN XY: 74324

African (AFR) AF: 0.290 AC: 12033 AN: 41500

American (AMR) AF: 0.507 AC: 7743 AN: 15278

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

East Asian (EAS) AF: 0.458 AC: 2369 AN: 5168

South Asian (SAS) AF: 0.574 AC: 2766 AN: 4822

European-Finnish (FIN) AF: 0.516 AC: 5449 AN: 10560

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

European-Non Finnish (NFE) AF: 0.514 AC: 34895 AN: 67938

Other (OTH) AF: 0.501 AC: 1060 AN: 2114

Alfa AF: 0.475 Hom.: 2296

Bravo AF: 0.444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.30
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs3786536; hg19: chr19-42372457;