rs2294714

Positions:

• chr1-6197766-T-C

Variant summary

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

The NM_000983.4(RPL22):​c.13-10A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 1,563,072 control chromosomes in the GnomAD database, including 65,572 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 0.33 (8589 hom., cov: 33)
  • Exomes 𝑓: 0.28 (56983 hom.)
• Consequence: RPL22 NM_000983.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00003427
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

Genes affected

RPL22 (HGNC:10315): (ribosomal protein L22) 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 cytoplasmic ribosomal protein that is a component of the 60S subunit. The protein belongs to the L22E family of ribosomal proteins. Its initiating methionine residue is post-translationally removed. The protein can bind specifically to Epstein-Barr virus-encoded RNAs (EBERs) 1 and 2. The mouse protein has been shown to be capable of binding to heparin. Transcript variants utilizing alternative polyA signals exist. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. It was previously thought that this gene mapped to 3q26 and that it was fused to the acute myeloid leukemia 1 (AML1) gene located at 21q22 in some therapy-related myelodysplastic syndrome patients with 3;21 translocations; however, these fusions actually involve a ribosomal protein L22 pseudogene located at 3q26, and this gene actually maps to 1p36.3-p36.2. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPL22	NM_000983.4	c.13-10A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000234875.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPL22	ENST00000234875.9	c.13-10A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000983.4	P1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49468 AN: 151898 Hom.: 8563 Cov.: 33

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.310

GnomAD3 exomes AF: 0.312 AC: 77373 AN: 248234 Hom.: 12828 AF XY: 0.304 AC XY: 40856 AN XY: 134236

Gnomad AFR exome AF: 0.436

Gnomad AMR exome AF: 0.362

Gnomad ASJ exome AF: 0.214

Gnomad EAS exome AF: 0.464

Gnomad SAS exome AF: 0.296

Gnomad FIN exome AF: 0.376

Gnomad NFE exome AF: 0.256

Gnomad OTH exome AF: 0.279

GnomAD4 exome AF: 0.281 AC: 396087 AN: 1411056 Hom.: 56983 Cov.: 26 AF XY: 0.280 AC XY: 197061 AN XY: 704438

Gnomad4 AFR exome AF: 0.439

Gnomad4 AMR exome AF: 0.355

Gnomad4 ASJ exome AF: 0.215

Gnomad4 EAS exome AF: 0.436

Gnomad4 SAS exome AF: 0.298

Gnomad4 FIN exome AF: 0.371

Gnomad4 NFE exome AF: 0.262

Gnomad4 OTH exome AF: 0.284

GnomAD4 genome AF: 0.326 AC: 49547 AN: 152016 Hom.: 8589 Cov.: 33 AF XY: 0.332 AC XY: 24659 AN XY: 74306

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.455

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.314

Alfa AF: 0.270 Hom.: 1567

Bravo AF: 0.326

Asia WGS AF: 0.345 AC: 1201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.84
DANN	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000034
dbscSNV1_RF	Benign	0.0040
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: rs2294714; hg19: chr1-6257826; COSMIC: COSV52378823; COSMIC: COSV52378823;