rs2075752

Variant names:

• chr19-41870766-G-A
• rs2075752
• NM_001022.4:c.412-585G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-41870766-G-A
• chr19-41870766-G-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001022.4(RPS19):​c.412-585G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000166 in 150,518 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: 𝑓 0.00017 (0 hom., cov: 27)
• Consequence: RPS19 NM_001022.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.294
• Publications: 7 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS2: High AC in GnomAd4 at 25 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS19	NM_001022.4	c.412-585G>A		intron_variant	Intron 5 of 5	ENST00000598742.6	NP_001013.1
RPS19	NM_001321485.2	c.425-585G>A		intron_variant	Intron 5 of 5		NP_001308414.1
RPS19	NM_001321483.2	c.412-585G>A		intron_variant	Intron 5 of 5		NP_001308412.1
RPS19	NM_001321484.2	c.412-585G>A		intron_variant	Intron 5 of 5		NP_001308413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS19	ENST00000598742.6	c.412-585G>A		intron_variant	Intron 5 of 5	1	NM_001022.4	ENSP00000470972.1
RPS19	ENST00000593863.5	c.412-585G>A		intron_variant	Intron 5 of 5	3		ENSP00000470004.1
RPS19	ENST00000600467.6	c.412-585G>A		intron_variant	Intron 5 of 5	2		ENSP00000469228.2
RPS19	ENST00000221975.6	c.190-585G>A		intron_variant	Intron 5 of 5	3		ENSP00000221975.2

Frequencies

GnomAD3 genomes AF: 0.000166 AC: 25 AN: 150518 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.000563

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000665

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000166 AC: 25 AN: 150518 Hom.: 0 Cov.: 27 AF XY: 0.000150 AC XY: 11 AN XY: 73328

African (AFR) AF: 0.000563 AC: 23 AN: 40842

American (AMR) AF: 0.0000665 AC: 1 AN: 15038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5094

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67802

Other (OTH) AF: 0.00 AC: 0 AN: 2062

Alfa AF: 0.00 Hom.: 7423

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
PhyloP100		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2075752; hg19: chr19-42374836;