1-23692589-G-T

Variant names:

• chr1-23692589-G-T
• rs142110379
• ENST00000458455.2:c.-47G>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The ENST00000458455.2(RPL11):​c.-47G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00261 in 1,613,932 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (6 hom.)
• Consequence: RPL11 ENST00000458455.2 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.25
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia 7

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• Diamond-Blackfan anemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-23692589-G-T is Benign according to our data. Variant chr1-23692589-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 285 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000458455.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL11	NM_000975.5	MANE Select	c.7-20G>T		intron	N/A	NP_000966.2
	RPL11	NM_001199802.1		c.7-23G>T		intron	N/A	NP_001186731.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL11	ENST00000458455.2	TSL:1	c.-47G>T		5_prime_UTR	Exon 1 of 5	ENSP00000398888.2
	RPL11	ENST00000643754.2	MANE Select	c.7-20G>T		intron	N/A	ENSP00000496250.1
	RPL11	ENST00000374550.8	TSL:1	c.7-23G>T		intron	N/A	ENSP00000363676.4

Frequencies

GnomAD3 genomes AF: 0.00187 AC: 285 AN: 152138 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.00293

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00214 AC: 538 AN: 251400 AF XY: 0.00235

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.00156

Gnomad ASJ exome AF: 0.00298

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00321

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00269 AC: 3935 AN: 1461676 Hom.: 6 Cov.: 31 AF XY: 0.00271 AC XY: 1967 AN XY: 727154

African (AFR) AF: 0.000359 AC: 12 AN: 33462

American (AMR) AF: 0.00165 AC: 74 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00337 AC: 88 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00227 AC: 196 AN: 86230

European-Finnish (FIN) AF: 0.000262 AC: 14 AN: 53350

Middle Eastern (MID) AF: 0.00364 AC: 21 AN: 5764

European-Non Finnish (NFE) AF: 0.00303 AC: 3372 AN: 1111936

Other (OTH) AF: 0.00262 AC: 158 AN: 60390

GnomAD4 genome AF: 0.00187 AC: 285 AN: 152256 Hom.: 0 Cov.: 32 AF XY: 0.00185 AC XY: 138 AN XY: 74454

African (AFR) AF: 0.000313 AC: 13 AN: 41528

American (AMR) AF: 0.00314 AC: 48 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4824

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10612

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.00293 AC: 199 AN: 68024

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00260 Hom.: 0

Bravo AF: 0.00172

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Jun 15, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Diamond-Blackfan anemia Benign:2

Jun 01, 2015

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely 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.

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Diamond-Blackfan anemia 7 Benign:1

Dec 13, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.8
DANN	Benign	0.69
PhyloP100		1.3
PromoterAI		-0.0059	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

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: rs142110379; hg19: chr1-24019079;