10-78033793-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1

The ENST00000613865.5(RPS24):c.-109A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0419 in 1,498,660 control chromosomes in the GnomAD database, including 2,891 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.046 ( 343 hom., cov: 32)

Exomes 𝑓: 0.041 ( 2548 hom. )

Consequence

RPS24
ENST00000613865.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: 0.363

Variant links:

Genes affected

RPS24 (HGNC:10411): (ribosomal protein S24) 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 40S subunit. The protein belongs to the S24E family of ribosomal proteins. It is located in the cytoplasm. Multiple 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. Mutations in this gene result in Diamond-Blackfan anemia. [provided by RefSeq, Nov 2008]

RPS24 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 10-78033793-A-G is Benign according to our data. Variant chr10-78033793-A-G is described in ClinVar as [Benign]. Clinvar id is 301088.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Appris	UniProt
RPS24	ENST00000435275.5 linkuse as main transcript	c.-109A>G	5_prime_UTR_variant	1/6	2	A1
RPS24	ENST00000613865.5 linkuse as main transcript	c.-109A>G	5_prime_UTR_variant	1/5	5	A1	P62847-1
RPS24	ENST00000645440.1 linkuse as main transcript		upstream_gene_variant			A1

Frequencies

GnomAD3 genomes

AF:

0.0457

AC:

6948

AN:

152110

Hom.:

343

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0303

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.0959

Gnomad ASJ

AF:

0.0113

Gnomad EAS

AF:

0.236

Gnomad SAS

AF:

0.156

Gnomad FIN

AF:

0.0314

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0256

Gnomad OTH

AF:

0.0458

GnomAD4 exome

AF:

0.0415

AC:

55864

AN:

1346432

Hom.:

2548

Cov.:

AF XY:

0.0438

AC XY:

29627

AN XY:

675988

show subpopulations

Gnomad4 AFR exome

AF:

0.0298

Gnomad4 AMR exome

AF:

0.0961

Gnomad4 ASJ exome

AF:

0.0106

Gnomad4 EAS exome

AF:

0.215

Gnomad4 SAS exome

AF:

0.135

Gnomad4 FIN exome

AF:

0.0345

Gnomad4 NFE exome

AF:

0.0257

Gnomad4 OTH exome

AF:

0.0505

GnomAD4 genome

AF:

0.0457

AC:

6961

AN:

152228

Hom.:

343

Cov.:

AF XY:

0.0503

AC XY:

3741

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0303

Gnomad4 AMR

AF:

0.0963

Gnomad4 ASJ

AF:

0.0113

Gnomad4 EAS

AF:

0.236

Gnomad4 SAS

AF:

0.156

Gnomad4 FIN

AF:

0.0314

Gnomad4 NFE

AF:

0.0256

Gnomad4 OTH

AF:

0.0506

Alfa

AF:

0.0123

Hom.:

Bravo

AF:

0.0469

Asia WGS

AF:

0.197

AC:

686

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Pol III-related leukodystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Diamond-Blackfan anemia 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Diamond-Blackfan anemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

Cadd

Benign

Dann

Benign

0.79

Splicing

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