rs2075749

Variant names:

• chr19-41860935-C-A
• rs2075749
• NM_001022.4:c.71+90C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-41860935-C-A
• chr19-41860935-C-G
• chr19-41860935-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001022.4(RPS19):​c.71+90C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000868 in 1,152,010 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 8.7e-7 (0 hom.)
• Consequence: RPS19 NM_001022.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.739
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (Cadd=1.264).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS19	NM_001022.4	c.71+90C>A		intron_variant	Intron 2 of 5	ENST00000598742.6	NP_001013.1
RPS19	NM_001321485.2	c.71+90C>A		intron_variant	Intron 2 of 5		NP_001308414.1
RPS19	NM_001321483.2	c.71+90C>A		intron_variant	Intron 2 of 5		NP_001308412.1
RPS19	NM_001321484.2	c.71+90C>A		intron_variant	Intron 2 of 5		NP_001308413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS19	ENST00000598742.6	c.71+90C>A		intron_variant	Intron 2 of 5	1	NM_001022.4	ENSP00000470972.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.68e-7 AC: 1 AN: 1152010 Hom.: 0 Cov.: 16 AF XY: 0.00 AC XY: 0 AN XY: 587310

African (AFR) AF: 0.00 AC: 0 AN: 27316

American (AMR) AF: 0.00 AC: 0 AN: 43878

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24296

East Asian (EAS) AF: 0.00 AC: 0 AN: 38188

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 80000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52948

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3566

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 831908

Other (OTH) AF: 0.00 AC: 0 AN: 49910

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	1.3
PhyloP100		-0.74
PromoterAI		-0.049	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2075749; hg19: -;