rs61761236

Positions:

• chr19-41864487-A-ACCACC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001022.4(RPS19):​c.172+3276_172+3280dup 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

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1716 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS19	NM_001022.4	c.172+3276_172+3280dup		intron_variant		ENST00000598742.6
RPS19	NM_001321483.2	c.172+3276_172+3280dup		intron_variant
RPS19	NM_001321484.2	c.172+3276_172+3280dup		intron_variant
RPS19	NM_001321485.2	c.185+3263_185+3267dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS19	ENST00000598742.6	c.172+3276_172+3280dup		intron_variant		1	NM_001022.4	P1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0135

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.00250

Gnomad4 AMR AF: 0.00956

Gnomad4 ASJ AF: 0.0124

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.00519

Gnomad4 NFE AF: 0.0192

Gnomad4 OTH AF: 0.0137

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 v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs61761236; hg19: chr19-42368557;