11-119018475-T-C

Variant names:

• chr11-119018475-T-C
• rs11217125
• ENST00000524864.1:n.192A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000527791.5(RPS25):​n.-191A>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 0.261 in 751,086 control chromosomes in the GnomAD database, including 27,014 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6446 hom., cov: 35)
  • Exomes 𝑓: 0.26 (20568 hom.)
• Consequence: RPS25 ENST00000527791.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.89

Genes affected

RPS25 (HGNC:10413): (ribosomal protein S25) 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 S25E family of ribosomal proteins. It is located in the cytoplasm. 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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-119018475-T-C is Benign according to our data. Variant chr11-119018475-T-C is described in ClinVar as [Benign]. Clinvar id is 1226681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS25	NM_001028.3	c.-191A>G		upstream_gene_variant		ENST00000527673.2	NP_001019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS25	ENST00000527673.2	c.-191A>G		upstream_gene_variant		1	NM_001028.3	ENSP00000435096.1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42785 AN: 152008 Hom.: 6423 Cov.: 35

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.0737

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.275

GnomAD4 exome AF: 0.256 AC: 153154 AN: 598960 Hom.: 20568 Cov.: 8 AF XY: 0.259 AC XY: 81282 AN XY: 314256

Gnomad4 AFR exome AF: 0.375 AC: 5659 AN: 15086

Gnomad4 AMR exome AF: 0.200 AC: 4649 AN: 23286

Gnomad4 ASJ exome AF: 0.210 AC: 3346 AN: 15906

Gnomad4 EAS exome AF: 0.101 AC: 3244 AN: 32186

Gnomad4 SAS exome AF: 0.317 AC: 16837 AN: 53178

Gnomad4 FIN exome AF: 0.261 AC: 8481 AN: 32490

Gnomad4 NFE exome AF: 0.260 AC: 101958 AN: 392552

Gnomad4 Remaining exome AF: 0.265 AC: 8276 AN: 31270

GnomAD4 genome AF: 0.282 AC: 42849 AN: 152126 Hom.: 6446 Cov.: 35 AF XY: 0.280 AC XY: 20809 AN XY: 74344

Gnomad4 AFR AF: 0.379 AC: 0.378513 AN: 0.378513

Gnomad4 AMR AF: 0.236 AC: 0.235737 AN: 0.235737

Gnomad4 ASJ AF: 0.196 AC: 0.196254 AN: 0.196254

Gnomad4 EAS AF: 0.0738 AC: 0.0738307 AN: 0.0738307

Gnomad4 SAS AF: 0.329 AC: 0.328773 AN: 0.328773

Gnomad4 FIN AF: 0.273 AC: 0.273449 AN: 0.273449

Gnomad4 NFE AF: 0.252 AC: 0.252192 AN: 0.252192

Gnomad4 OTH AF: 0.278 AC: 0.277673 AN: 0.277673

Alfa AF: 0.261 Hom.: 13249

Bravo AF: 0.279

Asia WGS AF: 0.239 AC: 835 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.24
DANN	Benign	0.39
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs11217125; hg19: chr11-118889185;