rs7254214

Positions:

• chr19-41864668-G-A
• chr19-41864668-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001022.4(RPS19):​c.172+3456G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 152,140 control chromosomes in the GnomAD database, including 15,200 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 0.42 (15190 hom., cov: 31)
  • Exomes 𝑓: 0.41 (10 hom.)
• Consequence: RPS19 NM_001022.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS19	NM_001022.4	c.172+3456G>A		intron_variant		ENST00000598742.6	NP_001013.1
RPS19	NM_001321485.2	c.185+3443G>A		intron_variant			NP_001308414.1
RPS19	NM_001321483.2	c.172+3456G>A		intron_variant			NP_001308412.1
RPS19	NM_001321484.2	c.172+3456G>A		intron_variant			NP_001308413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS19	ENST00000598742.6	c.172+3456G>A		intron_variant		1	NM_001022.4	ENSP00000470972.1

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63089 AN: 151902 Hom.: 15193 Cov.: 31

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.678

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.475

GnomAD4 exome AF: 0.408 AC: 49 AN: 120 Hom.: 10 Cov.: 0 AF XY: 0.330 AC XY: 29 AN XY: 88

Gnomad4 AFR exome AF: 0.167

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.398

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.415 AC: 63089 AN: 152020 Hom.: 15190 Cov.: 31 AF XY: 0.420 AC XY: 31228 AN XY: 74308

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.614

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.516

Gnomad4 NFE AF: 0.513

Gnomad4 OTH AF: 0.470

Alfa AF: 0.513 Hom.: 23189

Bravo AF: 0.398

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.23

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7254214; hg19: chr19-42368738;