1-23694734-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000975.5(RPL11):c.339C>T(p.Ile113=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0357 in 1,614,106 control chromosomes in the GnomAD database, including 1,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (69 hom., cov: 32)
  • Exomes 𝑓: 0.037 (1225 hom.)
• Consequence: RPL11 NM_000975.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0180

Genes affected

RPL11 (HGNC:10301): (ribosomal protein L11) 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 60S subunit. The protein belongs to the L5P family of ribosomal proteins. It is located in the cytoplasm. The protein probably associates with the 5S rRNA. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 1-23694734-C-T is Benign according to our data. Variant chr1-23694734-C-T is described in ClinVar as [Benign]. Clinvar id is 296821.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-23694734-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.018 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0249 (3793/152276) while in subpopulation NFE AF= 0.0393 (2671/68014). AF 95% confidence interval is 0.038. There are 69 homozygotes in gnomad4. There are 1751 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 3795 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPL11	NM_000975.5	c.339C>T	p.Ile113=	synonymous_variant	4/6	ENST00000643754.2
RPL11	NM_001199802.1	c.336C>T	p.Ile112=	synonymous_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPL11	ENST00000643754.2	c.339C>T	p.Ile113=	synonymous_variant	4/6		NM_000975.5	A1

Frequencies

GnomAD3 genomes AF: 0.0249 AC: 3795 AN: 152158 Hom.: 69 Cov.: 32

Gnomad AFR AF: 0.00777

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.0174

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.00539

Gnomad FIN AF: 0.0335

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0393

Gnomad OTH AF: 0.0234

GnomAD3 exomes AF: 0.0246 AC: 6180 AN: 251458 Hom.: 115 AF XY: 0.0242 AC XY: 3291 AN XY: 135906

Gnomad AFR exome AF: 0.00615

Gnomad AMR exome AF: 0.0125

Gnomad ASJ exome AF: 0.0113

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.00702

Gnomad FIN exome AF: 0.0354

Gnomad NFE exome AF: 0.0387

Gnomad OTH exome AF: 0.0236

GnomAD4 exome AF: 0.0368 AC: 53781 AN: 1461830 Hom.: 1225 Cov.: 31 AF XY: 0.0356 AC XY: 25895 AN XY: 727212

Gnomad4 AFR exome AF: 0.00565

Gnomad4 AMR exome AF: 0.0135

Gnomad4 ASJ exome AF: 0.0110

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00796

Gnomad4 FIN exome AF: 0.0330

Gnomad4 NFE exome AF: 0.0433

Gnomad4 OTH exome AF: 0.0330

GnomAD4 genome AF: 0.0249 AC: 3793 AN: 152276 Hom.: 69 Cov.: 32 AF XY: 0.0235 AC XY: 1751 AN XY: 74462

Gnomad4 AFR AF: 0.00775

Gnomad4 AMR AF: 0.0173

Gnomad4 ASJ AF: 0.0147

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.00539

Gnomad4 FIN AF: 0.0335

Gnomad4 NFE AF: 0.0393

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.0283 Hom.: 41

Bravo AF: 0.0226

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Diamond-Blackfan anemia Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	May 25, 2017	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Diamond-Blackfan anemia 7 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	12
Dann	Benign	0.56
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7

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: rs8880; hg19: chr1-24021224;