rs61762299

Positions:

• chr19-41871323-AC-A

Variant summary

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

The ENST00000598742.6(RPS19):​c.412-27del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000459 in 1,460,820 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000046 (0 hom.)
• Consequence: RPS19 ENST00000598742.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.414

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_exome allele frequency = 0.0000459 (67/1460820) while in subpopulation NFE AF= 0.0000504 (56/1111046). AF 95% confidence interval is 0.0000398. There are 0 homozygotes in gnomad4_exome. There are 31 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAdExome4 at 67 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS19	NM_001022.4	c.412-27del		intron_variant		ENST00000598742.6	NP_001013.1
RPS19	NM_001321483.2	c.412-27del		intron_variant			NP_001308412.1
RPS19	NM_001321484.2	c.412-27del		intron_variant			NP_001308413.1
RPS19	NM_001321485.2	c.425-27del		intron_variant			NP_001308414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS19	ENST00000598742.6	c.412-27del		intron_variant		1	NM_001022.4	ENSP00000470972	P1
RPS19	ENST00000221975.6	c.190-27del		intron_variant		3		ENSP00000221975
RPS19	ENST00000593863.5	c.412-27del		intron_variant		3		ENSP00000470004	P1
RPS19	ENST00000600467.6	c.412-27del		intron_variant		2		ENSP00000469228	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000557 AC: 14 AN: 251432 Hom.: 0 AF XY: 0.0000442 AC XY: 6 AN XY: 135874

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000459 AC: 67 AN: 1460820 Hom.: 0 Cov.: 30 AF XY: 0.0000427 AC XY: 31 AN XY: 726822

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000504

Gnomad4 OTH exome AF: 0.000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
La Branchor		0.71
BranchPoint Hunter		3.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs61762299; hg19: chr19-42375391;