rs12461099

Variant names:

• chr19-41861895-T-C
• rs12461099
• NM_001022.4:c.172+683T>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.172+683T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 152,050 control chromosomes in the GnomAD database, including 15,245 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 (15245 hom., cov: 32)
• Consequence: RPS19 NM_001022.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.607
• Publications: 3 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 (Cadd=1.398).
• 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.172+683T>C		intron_variant	Intron 3 of 5	ENST00000598742.6	NP_001013.1
RPS19	NM_001321485.2	c.185+670T>C		intron_variant	Intron 3 of 5		NP_001308414.1
RPS19	NM_001321483.2	c.172+683T>C		intron_variant	Intron 3 of 5		NP_001308412.1
RPS19	NM_001321484.2	c.172+683T>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.172+683T>C		intron_variant	Intron 3 of 5	1	NM_001022.4	ENSP00000470972.1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63412 AN: 151930 Hom.: 15247 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.477

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

GnomAD4 genome AF: 0.417 AC: 63416 AN: 152050 Hom.: 15245 Cov.: 32 AF XY: 0.422 AC XY: 31392 AN XY: 74308

African (AFR) AF: 0.161 AC: 6666 AN: 41520

American (AMR) AF: 0.491 AC: 7491 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2128 AN: 3466

East Asian (EAS) AF: 0.460 AC: 2381 AN: 5174

South Asian (SAS) AF: 0.572 AC: 2752 AN: 4812

European-Finnish (FIN) AF: 0.515 AC: 5443 AN: 10560

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34847 AN: 67942

Other (OTH) AF: 0.472 AC: 994 AN: 2108

Alfa AF: 0.495 Hom.: 9868

Bravo AF: 0.400

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	1.4
PhyloP100		-0.61

Splicing

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

Other links and lift over

dbSNP: rs12461099; hg19: -;