19-41864012-T-G

Variant names:

• chr19-41864012-T-G
• rs61761234
• NM_001022.4:c.172+2800T>G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001022.4(RPS19):​c.172+2800T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00487 in 152,050 control chromosomes in the GnomAD database, including 4 homozygotes. 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 0.0049 (4 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RPS19 NM_001022.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BS2: High AC in GnomAd4 at 740 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS19	NM_001022.4	c.172+2800T>G		intron_variant	Intron 3 of 5	ENST00000598742.6	NP_001013.1
RPS19	NM_001321485.2	c.185+2787T>G		intron_variant	Intron 3 of 5		NP_001308414.1
RPS19	NM_001321483.2	c.172+2800T>G		intron_variant	Intron 3 of 5		NP_001308412.1
RPS19	NM_001321484.2	c.172+2800T>G		intron_variant	Intron 3 of 5		NP_001308413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS19	ENST00000598742.6	c.172+2800T>G		intron_variant	Intron 3 of 5	1	NM_001022.4	ENSP00000470972.1

Frequencies

GnomAD3 genomes AF: 0.00488 AC: 741 AN: 151932 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.00164

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.00826

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.000473

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00706

Gnomad OTH AF: 0.00624

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 72 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 50

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00487 AC: 740 AN: 152050 Hom.: 4 Cov.: 31 AF XY: 0.00478 AC XY: 355 AN XY: 74324

Gnomad4 AFR AF: 0.00164

Gnomad4 AMR AF: 0.00825

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000624

Gnomad4 FIN AF: 0.000473

Gnomad4 NFE AF: 0.00705

Gnomad4 OTH AF: 0.00618

Alfa AF: 0.0000702 Hom.: 0

Bravo AF: 0.00584

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs61761234; hg19: chr19-42368082;