rs61761218

chr19-41860383-C-Gchr19-41860383-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001022.4(RPS19):c.-1+94C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00321 in 163,692 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0050 (1 hom.)
• Consequence: RPS19 NM_001022.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.582

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 19-41860383-C-G is Benign according to our data. Variant chr19-41860383-C-G is described in ClinVar as [Benign]. Clinvar id is 1239177.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00308 (468/152126) while in subpopulation SAS AF= 0.00972 (47/4834). AF 95% confidence interval is 0.00751. There are 1 homozygotes in gnomad4. There are 243 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 467 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS19	NM_001022.4	c.-1+94C>G		intron_variant		ENST00000598742.6
RPS19	NM_001321484.2	c.-63C>G		5_prime_UTR_variant	1/6
RPS19	NM_001321485.2	c.-1+94C>G		intron_variant
RPS19	NM_001321483.2			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS19	ENST00000598742.6	c.-1+94C>G		intron_variant		1	NM_001022.4	P1

Frequencies

GnomAD3 genomes AF: 0.00307 AC: 467 AN: 152018 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00302

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00971

Gnomad FIN AF: 0.00597

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00387

Gnomad OTH AF: 0.00478

GnomAD4 exome AF: 0.00501 AC: 58 AN: 11566 Hom.: 1 Cov.: 0 AF XY: 0.00529 AC XY: 32 AN XY: 6052

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00847

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0110

Gnomad4 FIN exome AF: 0.00584

Gnomad4 NFE exome AF: 0.00515

Gnomad4 OTH exome AF: 0.00386

GnomAD4 genome AF: 0.00308 AC: 468 AN: 152126 Hom.: 1 Cov.: 33 AF XY: 0.00327 AC XY: 243 AN XY: 74382

Gnomad4 AFR AF: 0.000481

Gnomad4 AMR AF: 0.00301

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00972

Gnomad4 FIN AF: 0.00597

Gnomad4 NFE AF: 0.00388

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00106 Hom.: 0

Bravo AF: 0.00249

Asia WGS AF: 0.00494 AC: 17 AN: 3456

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	14
Dann	Benign	0.66

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: rs61761218; hg19: chr19-42364453;