chr1-23692463-T-C

Variant names:

• chr1-23692463-T-C
• rs78796509
• ENST00000458455.2:c.-173T>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.-173T>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 0.0177 in 975,720 control chromosomes in the GnomAD database, including 354 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: 0.015 (177 hom.)
• Consequence: RPL11 ENST00000458455.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0720
• 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 1-23692463-T-C is Benign according to our data. Variant chr1-23692463-T-C is described in ClinVar as Benign. ClinVar VariationId is 1251916.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.7-146T>C		intron	N/A	NP_000966.2
	RPL11	NM_001199802.1		c.7-149T>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.-173T>C		5_prime_UTR	Exon 1 of 5	ENSP00000398888.2	Q5VVC8
	RPL11	ENST00000643754.2	MANE Select	c.7-146T>C		intron	N/A	ENSP00000496250.1	P62913-1
	RPL11	ENST00000374550.8	TSL:1	c.7-149T>C		intron	N/A	ENSP00000363676.4	P62913-2

Frequencies

GnomAD3 genomes AF: 0.0343 AC: 5217 AN: 152128 Hom.: 176 Cov.: 32

Gnomad AFR AF: 0.0858

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0247

Gnomad ASJ AF: 0.00979

Gnomad EAS AF: 0.0419

Gnomad SAS AF: 0.00848

Gnomad FIN AF: 0.00914

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0117

Gnomad OTH AF: 0.0350

GnomAD4 exome AF: 0.0146 AC: 11992 AN: 823474 Hom.: 177 Cov.: 11 AF XY: 0.0141 AC XY: 5977 AN XY: 424394

African (AFR) AF: 0.0844 AC: 1753 AN: 20774

American (AMR) AF: 0.0166 AC: 550 AN: 33232

Ashkenazi Jewish (ASJ) AF: 0.00774 AC: 152 AN: 19648

East Asian (EAS) AF: 0.0373 AC: 1276 AN: 34170

South Asian (SAS) AF: 0.00886 AC: 581 AN: 65566

European-Finnish (FIN) AF: 0.0102 AC: 386 AN: 37886

Middle Eastern (MID) AF: 0.0390 AC: 125 AN: 3208

European-Non Finnish (NFE) AF: 0.0110 AC: 6280 AN: 570328

Other (OTH) AF: 0.0230 AC: 889 AN: 38662

GnomAD4 genome AF: 0.0344 AC: 5234 AN: 152246 Hom.: 177 Cov.: 32 AF XY: 0.0329 AC XY: 2447 AN XY: 74450

African (AFR) AF: 0.0859 AC: 3567 AN: 41516

American (AMR) AF: 0.0247 AC: 377 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00979 AC: 34 AN: 3472

East Asian (EAS) AF: 0.0418 AC: 217 AN: 5188

South Asian (SAS) AF: 0.00828 AC: 40 AN: 4832

European-Finnish (FIN) AF: 0.00914 AC: 97 AN: 10610

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0117 AC: 796 AN: 68020

Other (OTH) AF: 0.0361 AC: 76 AN: 2108

Alfa AF: 0.0279 Hom.: 16

Bravo AF: 0.0367

Asia WGS AF: 0.0410 AC: 142 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	6.8
DANN	Benign	0.42
PhyloP100		-0.072
PromoterAI		0.019	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: rs78796509; hg19: chr1-24018953;