1-23694734-C-T

Position:

chr1-23694734-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0180

Variant links:

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]

RPL11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 GnomAd4 at 3793 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL11	NM_000975.5 linkuse as main transcript	c.339C>T	p.Ile113=	synonymous_variant	4/6	ENST00000643754.2	NP_000966.2
RPL11	NM_001199802.1 linkuse as main transcript	c.336C>T	p.Ile112=	synonymous_variant	4/6		NP_001186731.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL11	ENST00000643754.2 linkuse as main transcript	c.339C>T	p.Ile113=	synonymous_variant	4/6		NM_000975.5	ENSP00000496250	A1	P62913-1

Frequencies

GnomAD3 genomes

AF:

0.0249

AC:

3795

AN:

152158

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0356

AC XY:

25895

AN XY:

727212

show subpopulations

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.:

Cov.:

AF XY:

0.0235

AC XY:

1751

AN XY:

74462

show subpopulations

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.:

Bravo

AF:

0.0226

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Diamond-Blackfan anemia

Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over