rs61761236

Variant names:

• chr19-41864487-A-ACCACC
• rs61761236
• NM_001022.4:c.172+3276_172+3280dupCCACC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001022.4(RPS19):​c.172+3276_172+3280dupCCACC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 152,266 control chromosomes in the GnomAD database, including 12 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.011 (12 hom., cov: 31)
  • Exomes 𝑓: 0.010 (0 hom.)
• Consequence: RPS19 NM_001022.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970
• Publications: 1 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: Orphanet, ClinGen
• Diamond-Blackfan anemia 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0113 (1716/152168) while in subpopulation NFE AF = 0.0192 (1306/68006). AF 95% confidence interval is 0.0183. There are 12 homozygotes in GnomAd4. There are 795 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1716 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001022.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS19	NM_001022.4	MANE Select	c.172+3276_172+3280dupCCACC		intron	N/A	NP_001013.1	B0ZBD0
	RPS19	NM_001321485.2		c.185+3263_185+3267dupCCACC		intron	N/A	NP_001308414.1
	RPS19	NM_001321483.2		c.172+3276_172+3280dupCCACC		intron	N/A	NP_001308412.1	B0ZBD0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS19	ENST00000598742.6	TSL:1 MANE Select	c.172+3276_172+3280dupCCACC		intron	N/A	ENSP00000470972.1	P39019
	RPS19	ENST00000593863.5	TSL:3	c.172+3276_172+3280dupCCACC		intron	N/A	ENSP00000470004.1	P39019
	RPS19	ENST00000600467.6	TSL:2	c.172+3276_172+3280dupCCACC		intron	N/A	ENSP00000469228.2	P39019

Frequencies

GnomAD3 genomes AF: 0.0113 AC: 1714 AN: 152050 Hom.: 12 Cov.: 31

Gnomad AFR AF: 0.00251

Gnomad AMI AF: 0.0187

Gnomad AMR AF: 0.00958

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00519

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0192

Gnomad OTH AF: 0.0134

GnomAD4 exome AF: 0.0102 AC: 1 AN: 98 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 68

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0135 AC: 1 AN: 74

Other (OTH) AF: 0.00 AC: 0 AN: 8

GnomAD4 genome AF: 0.0113 AC: 1716 AN: 152168 Hom.: 12 Cov.: 31 AF XY: 0.0107 AC XY: 795 AN XY: 74400

African (AFR) AF: 0.00250 AC: 104 AN: 41520

American (AMR) AF: 0.00956 AC: 146 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 43 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4814

European-Finnish (FIN) AF: 0.00519 AC: 55 AN: 10598

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0192 AC: 1306 AN: 68006

Other (OTH) AF: 0.0137 AC: 29 AN: 2112

Alfa AF: 0.0149 Hom.: 3

Bravo AF: 0.0111

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.097
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs61761236; hg19: chr19-42368557;