1-23692475-T-G

Variant names:

• chr1-23692475-T-G
• rs79924731
• ENST00000458455.2:c.-161T>G

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.-161T>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 1,164,680 control chromosomes in the GnomAD database, including 400 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (177 hom., cov: 32)
  • Exomes 𝑓: 0.014 (223 hom.)
• Consequence: RPL11 ENST00000458455.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.179
• 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=-0.83).
• BP6: Variant 1-23692475-T-G is Benign according to our data. Variant chr1-23692475-T-G is described in ClinVar as Benign. ClinVar VariationId is 1289189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0836 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.7-134T>G		intron	N/A	NP_000966.2
	RPL11	NM_001199802.1		c.7-137T>G		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.-161T>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000398888.2	Q5VVC8
	RPL11	ENST00000458455.2	TSL:1	c.-161T>G		5_prime_UTR	Exon 1 of 5	ENSP00000398888.2	Q5VVC8
	RPL11	ENST00000643754.2	MANE Select	c.7-134T>G		intron	N/A	ENSP00000496250.1	P62913-1

Frequencies

GnomAD3 genomes AF: 0.0342 AC: 5205 AN: 152100 Hom.: 176 Cov.: 32

Gnomad AFR AF: 0.0859

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0246

Gnomad ASJ AF: 0.00980

Gnomad EAS AF: 0.0421

Gnomad SAS AF: 0.00849

Gnomad FIN AF: 0.00906

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0116

Gnomad OTH AF: 0.0344

GnomAD4 exome AF: 0.0141 AC: 14296 AN: 1012462 Hom.: 223 Cov.: 13 AF XY: 0.0138 AC XY: 7143 AN XY: 518530

African (AFR) AF: 0.0846 AC: 2086 AN: 24660

American (AMR) AF: 0.0161 AC: 627 AN: 38840

Ashkenazi Jewish (ASJ) AF: 0.00793 AC: 176 AN: 22194

East Asian (EAS) AF: 0.0372 AC: 1361 AN: 36558

South Asian (SAS) AF: 0.00896 AC: 660 AN: 73684

European-Finnish (FIN) AF: 0.00996 AC: 434 AN: 43570

Middle Eastern (MID) AF: 0.0368 AC: 152 AN: 4128

European-Non Finnish (NFE) AF: 0.0107 AC: 7751 AN: 723390

Other (OTH) AF: 0.0231 AC: 1049 AN: 45438

GnomAD4 genome AF: 0.0343 AC: 5222 AN: 152218 Hom.: 177 Cov.: 32 AF XY: 0.0328 AC XY: 2439 AN XY: 74426

African (AFR) AF: 0.0860 AC: 3570 AN: 41514

American (AMR) AF: 0.0246 AC: 376 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00980 AC: 34 AN: 3468

East Asian (EAS) AF: 0.0420 AC: 218 AN: 5186

South Asian (SAS) AF: 0.00829 AC: 40 AN: 4824

European-Finnish (FIN) AF: 0.00906 AC: 96 AN: 10600

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0116 AC: 790 AN: 68022

Other (OTH) AF: 0.0355 AC: 75 AN: 2112

Alfa AF: 0.0193 Hom.: 23

Bravo AF: 0.0366

Asia WGS AF: 0.0400 AC: 140 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	-0.83
CADD	Benign	1.4
DANN	Benign	0.36
PhyloP100		0.18
PromoterAI		0.0066	Neutral
Mutation Taster		=100/0	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: rs79924731; hg19: chr1-24018965;