19-41860325-C-T

Variant names:

• chr19-41860325-C-T
• rs930102
• NM_001022.4:c.-1+36C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001321484.2(RPS19):​c.-121C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 153,960 control chromosomes in the GnomAD database, including 16,266 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 0.44 (15954 hom., cov: 34)
  • Exomes 𝑓: 0.56 (312 hom.)
• Consequence: RPS19 NM_001321484.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 6 publications found

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]

RPS19 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Diamond-Blackfan anemia 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ENSG00000306611 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321484.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS19	NM_001022.4	MANE Select	c.-1+36C>T		intron	N/A	NP_001013.1
	RPS19	NM_001321484.2		c.-121C>T		5_prime_UTR	Exon 1 of 6	NP_001308413.1
	RPS19	NM_001321485.2		c.-1+36C>T		intron	N/A	NP_001308414.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS19	ENST00000598742.6	TSL:1 MANE Select	c.-1+36C>T		intron	N/A	ENSP00000470972.1
	RPS19	ENST00000600467.6	TSL:2	c.-121C>T		5_prime_UTR	Exon 1 of 6	ENSP00000469228.2
	RPS19	ENST00000933915.1		c.-34+36C>T		intron	N/A	ENSP00000603974.1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66574 AN: 151966 Hom.: 15959 Cov.: 34

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.492

GnomAD4 exome AF: 0.557 AC: 1047 AN: 1880 Hom.: 312 Cov.: 0 AF XY: 0.560 AC XY: 594 AN XY: 1060

African (AFR) AF: 0.274 AC: 17 AN: 62

American (AMR) AF: 0.625 AC: 10 AN: 16

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 51 AN: 82

East Asian (EAS) AF: 0.538 AC: 42 AN: 78

South Asian (SAS) AF: 0.685 AC: 37 AN: 54

European-Finnish (FIN) AF: 0.548 AC: 183 AN: 334

Middle Eastern (MID) AF: 0.800 AC: 8 AN: 10

European-Non Finnish (NFE) AF: 0.558 AC: 638 AN: 1144

Other (OTH) AF: 0.610 AC: 61 AN: 100

GnomAD4 genome AF: 0.438 AC: 66578 AN: 152080 Hom.: 15954 Cov.: 34 AF XY: 0.443 AC XY: 32912 AN XY: 74364

African (AFR) AF: 0.231 AC: 9599 AN: 41504

American (AMR) AF: 0.500 AC: 7642 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2137 AN: 3470

East Asian (EAS) AF: 0.460 AC: 2378 AN: 5174

South Asian (SAS) AF: 0.571 AC: 2759 AN: 4828

European-Finnish (FIN) AF: 0.516 AC: 5460 AN: 10576

Middle Eastern (MID) AF: 0.685 AC: 200 AN: 292

European-Non Finnish (NFE) AF: 0.513 AC: 34862 AN: 67932

Other (OTH) AF: 0.487 AC: 1028 AN: 2112

Alfa AF: 0.464 Hom.: 2100

Bravo AF: 0.424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	4.4
PhyloP100		-1.1
PromoterAI		0.0074	Neutral

Splicing

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

Other links and lift over

dbSNP: rs930102; hg19: chr19-42364395;