1-6197766-T-C

Variant names:

• chr1-6197766-T-C
• rs2294714
• ENST00000480661.1:n.1798A>G

Variant summary

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

The ENST00000480661.1(RPL22):​n.1798A>G variant causes a non coding transcript exon 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 ENST00000480661.1 non_coding_transcript_exon
• Scores: Splicing: ADA: 0.00003427
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 8 publications found

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]

ENSG00000285629 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RPL22	NM_000983.4	c.13-10A>G		intron_variant	Intron 1 of 3	ENST00000234875.9	NP_000974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL22	ENST00000234875.9	c.13-10A>G		intron_variant	Intron 1 of 3	1	NM_000983.4	ENSP00000346088.3
ENSG00000285629	ENST00000484532.6	n.-97A>G		upstream_gene_variant		2		ENSP00000465763.1

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

GnomAD2 exomes AF: 0.312 AC: 77373 AN: 248234 AF XY: 0.304

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 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

African (AFR) AF: 0.439 AC: 14395 AN: 32794

American (AMR) AF: 0.355 AC: 15781 AN: 44426

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 5489 AN: 25538

East Asian (EAS) AF: 0.436 AC: 17247 AN: 39528

South Asian (SAS) AF: 0.298 AC: 25480 AN: 85390

European-Finnish (FIN) AF: 0.371 AC: 19408 AN: 52286

Middle Eastern (MID) AF: 0.281 AC: 1598 AN: 5688

European-Non Finnish (NFE) AF: 0.262 AC: 279994 AN: 1066692

Other (OTH) AF: 0.284 AC: 16695 AN: 58714

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

African (AFR) AF: 0.424 AC: 17576 AN: 41448

American (AMR) AF: 0.320 AC: 4886 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 711 AN: 3472

East Asian (EAS) AF: 0.455 AC: 2352 AN: 5174

South Asian (SAS) AF: 0.284 AC: 1368 AN: 4822

European-Finnish (FIN) AF: 0.390 AC: 4114 AN: 10556

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17523 AN: 67952

Other (OTH) AF: 0.314 AC: 663 AN: 2114

Alfa AF: 0.280 Hom.: 9001

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
PhyloP100		-1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2294714; hg19: chr1-6257826; COSMIC: COSV52378823; COSMIC: COSV52378823;