Genetic Variant ENST00000458455:c.-127T>C (chr1-23692509-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000458455(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 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.10

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL11	NM_000975.5 link	c.7-100T>C		intron_variant	Intron 1 of 5	ENST00000643754.2	NP_000966.2	P62913-1Q5VVD0
RPL11	NM_001199802.1 link	c.7-103T>C		intron_variant	Intron 1 of 5		NP_001186731.1	P62913-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL11	ENST00000643754.2 link	c.7-100T>C		intron_variant	Intron 1 of 5		NM_000975.5	ENSP00000496250.1		P62913-1

Frequencies

GnomAD3 genomes

AF:

0.0230

AC:

3497

AN:

152152

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.0116

AC XY:

7798

AN XY:

673056

show subpopulations

Gnomad4 AFR exome

AF:

0.0515

Gnomad4 AMR exome

AF:

0.00968

Gnomad4 ASJ exome

AF:

0.00300

Gnomad4 EAS exome

AF:

0.0376

Gnomad4 SAS exome

AF:

0.00837

Gnomad4 FIN exome

AF:

0.0100

Gnomad4 NFE exome

AF:

0.00988

Gnomad4 OTH exome

AF:

0.0168

GnomAD4 genome

AF:

0.0230

AC:

3504

AN:

152270

Hom.:

Cov.:

AF XY:

0.0216

AC XY:

1606

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0518

Gnomad4 AMR

AF:

0.0116

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.0420

Gnomad4 SAS

AF:

0.00830

Gnomad4 FIN

AF:

0.00913

Gnomad4 NFE

AF:

0.0108

Gnomad4 OTH

AF:

0.0251

Alfa

AF:

0.0166

Hom.:

Bravo

AF:

0.0243

Asia WGS

AF:

0.0300

AC:

105

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.72

DANN

Benign

0.47

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

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