19-41869609-T-C

Position:

• chr19-41869609-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
RPS19	NM_001022.4	c.357-90T>C		intron_variant		ENST00000598742.6
MIR6797	NR_106855.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS19	ENST00000598742.6	c.357-90T>C		intron_variant		1	NM_001022.4	P1
MIR6797	ENST00000621706.1			upstream_gene_variant

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

Gnomad4 AFR exome AF: 0.282

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.655

Gnomad4 EAS exome AF: 0.462

Gnomad4 SAS exome AF: 0.591

Gnomad4 FIN exome AF: 0.515

Gnomad4 NFE exome AF: 0.506

Gnomad4 OTH exome AF: 0.516

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

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.574

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.502

Alfa AF: 0.521 Hom.: 16693

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2075750; hg19: chr19-42373679;