rs114249836

Variant names:

• chr1-23692509-T-C
• rs114249836
• ENST00000458455.2:c.-127T>C

Variant summary

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

The ENST00000458455.2(RPL11):​c.-127T>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 0.0129 in 1,492,604 control chromosomes in the GnomAD database, including 238 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (67 hom., cov: 32)
  • Exomes 𝑓: 0.012 (171 hom.)
• Consequence: RPL11 ENST00000458455.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.10
• 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: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
• Diamond-Blackfan anemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-23692509-T-C is Benign according to our data. Variant chr1-23692509-T-C is described in ClinVar as Benign. ClinVar VariationId is 1266155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.05 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL11	NM_000975.5	MANE Select	c.7-100T>C		intron	N/A	NP_000966.2
	RPL11	NM_001199802.1		c.7-103T>C		intron	N/A	NP_001186731.1	P62913-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL11	ENST00000458455.2	TSL:1	c.-127T>C		5_prime_UTR	Exon 1 of 5	ENSP00000398888.2	Q5VVC8
	RPL11	ENST00000643754.2	MANE Select	c.7-100T>C		intron	N/A	ENSP00000496250.1	P62913-1
	RPL11	ENST00000374550.8	TSL:1	c.7-103T>C		intron	N/A	ENSP00000363676.4	P62913-2

Frequencies

GnomAD3 genomes AF: 0.0230 AC: 3497 AN: 152152 Hom.: 67 Cov.: 32

Gnomad AFR AF: 0.0518

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0117

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.0421

Gnomad SAS AF: 0.00850

Gnomad FIN AF: 0.00913

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.0253

GnomAD4 exome AF: 0.0118 AC: 15750 AN: 1340334 Hom.: 171 Cov.: 19 AF XY: 0.0116 AC XY: 7798 AN XY: 673056

African (AFR) AF: 0.0515 AC: 1599 AN: 31034

American (AMR) AF: 0.00968 AC: 429 AN: 44318

Ashkenazi Jewish (ASJ) AF: 0.00300 AC: 76 AN: 25302

East Asian (EAS) AF: 0.0376 AC: 1465 AN: 38956

South Asian (SAS) AF: 0.00837 AC: 695 AN: 83070

European-Finnish (FIN) AF: 0.0100 AC: 514 AN: 51372

Middle Eastern (MID) AF: 0.0195 AC: 106 AN: 5442

European-Non Finnish (NFE) AF: 0.00988 AC: 9924 AN: 1004658

Other (OTH) AF: 0.0168 AC: 942 AN: 56182

GnomAD4 genome AF: 0.0230 AC: 3504 AN: 152270 Hom.: 67 Cov.: 32 AF XY: 0.0216 AC XY: 1606 AN XY: 74468

African (AFR) AF: 0.0518 AC: 2154 AN: 41546

American (AMR) AF: 0.0116 AC: 178 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3470

East Asian (EAS) AF: 0.0420 AC: 218 AN: 5188

South Asian (SAS) AF: 0.00830 AC: 40 AN: 4820

European-Finnish (FIN) AF: 0.00913 AC: 97 AN: 10620

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0108 AC: 732 AN: 68016

Other (OTH) AF: 0.0251 AC: 53 AN: 2114

Alfa AF: 0.0177 Hom.: 9

Bravo AF: 0.0243

Asia WGS AF: 0.0300 AC: 105 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	-0.86
CADD	Benign	0.72
DANN	Benign	0.47
PhyloP100		-1.1
PromoterAI		-0.021	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs114249836; hg19: chr1-24018999;