19-41869823-T-C

Variant names:

• chr19-41869823-T-C
• rs2075751
• NM_001022.4:c.411+70T>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.411+70T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,520,068 control chromosomes in the GnomAD database, including 77,521 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 0.26 (6075 hom., cov: 32)
  • Exomes 𝑓: 0.32 (71446 hom.)
• Consequence: RPS19 NM_001022.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.337
• Publications: 17 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS19	NM_001022.4	c.411+70T>C		intron_variant	Intron 5 of 5	ENST00000598742.6	NP_001013.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS19	ENST00000598742.6	c.411+70T>C		intron_variant	Intron 5 of 5	1	NM_001022.4	ENSP00000470972.1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39070 AN: 152084 Hom.: 6076 Cov.: 32

Gnomad AFR AF: 0.0849

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.299

GnomAD4 exome AF: 0.318 AC: 435238 AN: 1367866 Hom.: 71446 AF XY: 0.322 AC XY: 220967 AN XY: 685384

African (AFR) AF: 0.0779 AC: 2460 AN: 31584

American (AMR) AF: 0.375 AC: 16593 AN: 44288

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 10423 AN: 25584

East Asian (EAS) AF: 0.195 AC: 7656 AN: 39240

South Asian (SAS) AF: 0.409 AC: 34463 AN: 84338

European-Finnish (FIN) AF: 0.287 AC: 15101 AN: 52664

Middle Eastern (MID) AF: 0.497 AC: 2780 AN: 5590

European-Non Finnish (NFE) AF: 0.319 AC: 328099 AN: 1027206

Other (OTH) AF: 0.308 AC: 17663 AN: 57372

GnomAD4 genome AF: 0.257 AC: 39064 AN: 152202 Hom.: 6075 Cov.: 32 AF XY: 0.261 AC XY: 19385 AN XY: 74408

African (AFR) AF: 0.0846 AC: 3516 AN: 41536

American (AMR) AF: 0.344 AC: 5259 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1410 AN: 3466

East Asian (EAS) AF: 0.184 AC: 955 AN: 5182

South Asian (SAS) AF: 0.390 AC: 1880 AN: 4818

European-Finnish (FIN) AF: 0.291 AC: 3085 AN: 10598

Middle Eastern (MID) AF: 0.452 AC: 132 AN: 292

European-Non Finnish (NFE) AF: 0.322 AC: 21858 AN: 67984

Other (OTH) AF: 0.296 AC: 626 AN: 2114

Alfa AF: 0.314 Hom.: 6785

Bravo AF: 0.249

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.5
PhyloP100		0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Other links and lift over

dbSNP: rs2075751; hg19: chr19-42373893;