Variant chr12-56042132-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001029.5(RPS26):c.-35G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00027 in 1,613,590 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00016 ( 1 hom. )

Consequence

RPS26
NM_001029.5 5_prime_UTR

Scores

Splicing: ADA: 0.00001354

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.96

Variant links:

Genes affected

RPS26 (HGNC:10414): (ribosomal protein S26) This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S26E family of ribosomal proteins. Mutations in this gene are found in Diamond-Blackfan anemia 10. There are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Aug 2017]

RPS26 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 12-56042132-G-A is Benign according to our data. Variant chr12-56042132-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 309853.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 195 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS26	NM_001029.5 link	c.-35G>A		5_prime_UTR_variant	1/4	ENST00000646449.2	NP_001020.2	P62854A0A024RB14

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RPS26	ENST00000646449 link	c.-35G>A	5_prime_UTR_variant	1/4		NM_001029.5	ENSP00000496643.1	P62854
RPS26	ENST00000356464 link	c.-35G>A	5_prime_UTR_variant	2/5	1		ENSP00000348849.5	P62854
RPS26	ENST00000552361.1 link	c.-34-1G>A	splice_acceptor_variant, intron_variant		5		ENSP00000450339.1	P62854
RPS26	ENST00000548590.1 link	n.-8G>A	upstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00127

AC:

193

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00437

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000318

AC:

AN:

251268

Hom.:

AF XY:

0.000258

AC XY:

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.00363

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000164

AC:

240

AN:

1461280

Hom.:

Cov.:

AF XY:

0.000154

AC XY:

112

AN XY:

726988

show subpopulations

Gnomad4 AFR exome

AF:

0.00496

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.000563

GnomAD4 genome

AF:

0.00128

AC:

195

AN:

152310

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00440

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000256

Hom.:

Bravo

AF:

0.00131

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 22, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Diamond-Blackfan anemia 10

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.075

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000014

dbscSNV1_RF

Benign

0.018

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

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