19-41869609-T-C

Variant names:

• chr19-41869609-T-C
• rs2075750
• NM_001022.4:c.357-90T>C

Variant summary

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

The NM_001022.4(RPS19):​c.357-90T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 1,460,462 control chromosomes in the GnomAD database, including 188,088 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 (16669 hom., cov: 31)
  • Exomes 𝑓: 0.51 (171419 hom.)
• Consequence: RPS19 NM_001022.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 10 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]

MIR6797 (HGNC:50169): (microRNA 6797) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• 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.357-90T>C		intron_variant	Intron 4 of 5	ENST00000598742.6	NP_001013.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS19	ENST00000598742.6	c.357-90T>C		intron_variant	Intron 4 of 5	1	NM_001022.4	ENSP00000470972.1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69150 AN: 151722 Hom.: 16654 Cov.: 31

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.507

GnomAD4 exome AF: 0.509 AC: 665558 AN: 1308622 Hom.: 171419 Cov.: 18 AF XY: 0.513 AC XY: 337463 AN XY: 657596

African (AFR) AF: 0.282 AC: 8580 AN: 30440

American (AMR) AF: 0.500 AC: 21873 AN: 43728

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 16416 AN: 25058

East Asian (EAS) AF: 0.462 AC: 17915 AN: 38738

South Asian (SAS) AF: 0.591 AC: 48969 AN: 82928

European-Finnish (FIN) AF: 0.515 AC: 23014 AN: 44686

Middle Eastern (MID) AF: 0.697 AC: 3194 AN: 4582

European-Non Finnish (NFE) AF: 0.506 AC: 497104 AN: 983208

Other (OTH) AF: 0.516 AC: 28493 AN: 55254

GnomAD4 genome AF: 0.456 AC: 69203 AN: 151840 Hom.: 16669 Cov.: 31 AF XY: 0.461 AC XY: 34181 AN XY: 74202

African (AFR) AF: 0.289 AC: 11988 AN: 41444

American (AMR) AF: 0.506 AC: 7718 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2270 AN: 3470

East Asian (EAS) AF: 0.460 AC: 2356 AN: 5126

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

European-Finnish (FIN) AF: 0.517 AC: 5450 AN: 10548

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

European-Non Finnish (NFE) AF: 0.514 AC: 34883 AN: 67880

Other (OTH) AF: 0.502 AC: 1057 AN: 2106

Alfa AF: 0.514 Hom.: 19667

Bravo AF: 0.444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.8
PhyloP100		-1.0

Splicing

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

Other links and lift over

dbSNP: rs2075750; hg19: chr19-42373679;