ENST00000937795.1:c.-138T>C

Variant names:

• chr11-119018422-A-G
• rs11217124
• ENST00000937795.1:c.-138T>C

Variant summary

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

The ENST00000937795.1(RPS25):​c.-138T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 1,253,290 control chromosomes in the GnomAD database, including 47,368 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7646 hom., cov: 36)
  • Exomes 𝑓: 0.26 (39722 hom.)
• Consequence: RPS25 ENST00000937795.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0770
• Publications: 8 publications found

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]

ENSG00000300421 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-119018422-A-G is Benign according to our data. Variant chr11-119018422-A-G is described in ClinVar as Benign. ClinVar VariationId is 1270573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000937795.1. 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
	RPS25	NM_001028.3	MANE Select	c.-138T>C		upstream_gene	N/A	NP_001019.1	P62851

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS25	ENST00000937795.1		c.-138T>C		5_prime_UTR	Exon 1 of 5	ENSP00000607854.1
	RPS25	ENST00000942362.1		c.-138T>C		5_prime_UTR	Exon 1 of 5	ENSP00000612421.1
	RPS25	ENST00000937796.1		c.-138T>C		5_prime_UTR	Exon 1 of 5	ENSP00000607855.1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45712 AN: 152138 Hom.: 7622 Cov.: 36

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.0736

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.286

GnomAD4 exome AF: 0.264 AC: 290445 AN: 1101034 Hom.: 39722 Cov.: 14 AF XY: 0.265 AC XY: 147284 AN XY: 556534

African (AFR) AF: 0.450 AC: 11197 AN: 24864

American (AMR) AF: 0.197 AC: 6615 AN: 33612

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 4815 AN: 22914

East Asian (EAS) AF: 0.0992 AC: 3433 AN: 34610

South Asian (SAS) AF: 0.318 AC: 23694 AN: 74584

European-Finnish (FIN) AF: 0.263 AC: 11403 AN: 43430

Middle Eastern (MID) AF: 0.251 AC: 1265 AN: 5042

European-Non Finnish (NFE) AF: 0.264 AC: 214954 AN: 813830

Other (OTH) AF: 0.271 AC: 13069 AN: 48148

GnomAD4 genome AF: 0.301 AC: 45779 AN: 152256 Hom.: 7646 Cov.: 36 AF XY: 0.298 AC XY: 22215 AN XY: 74444

African (AFR) AF: 0.445 AC: 18497 AN: 41540

American (AMR) AF: 0.243 AC: 3710 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 680 AN: 3470

East Asian (EAS) AF: 0.0738 AC: 383 AN: 5190

South Asian (SAS) AF: 0.329 AC: 1589 AN: 4830

European-Finnish (FIN) AF: 0.273 AC: 2894 AN: 10604

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17151 AN: 68010

Other (OTH) AF: 0.288 AC: 608 AN: 2112

Alfa AF: 0.279 Hom.: 2553

Bravo AF: 0.301

Asia WGS AF: 0.243 AC: 848 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.0
DANN	Benign	0.63
PhyloP100		-0.077
PromoterAI		0.21	Neutral
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

Other links and lift over

dbSNP: rs11217124; hg19: chr11-118889132;