Variant 12-56041958-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001029.5(RPS26):c.-209T>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 0.00105 in 661,084 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00087 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 7 hom. )

Consequence

RPS26
NM_001029.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.76

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 12-56041958-T-G is Benign according to our data. Variant chr12-56041958-T-G is described in ClinVar as [Benign]. Clinvar id is 309850.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000873 (133/152346) while in subpopulation EAS AF= 0.0241 (125/5188). AF 95% confidence interval is 0.0207. There are 2 homozygotes in gnomad4. There are 88 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 133 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS26	NM_001029.5 linkuse as main transcript	c.-209T>G		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 linkuse as main transcript	c.-209T>G	5_prime_UTR_variant	1/4		NM_001029.5	ENSP00000496643.1	P62854
RPS26	ENST00000356464 linkuse as main transcript	c.-209T>G	5_prime_UTR_variant	2/5	1		ENSP00000348849.5	P62854
RPS26	ENST00000552361 linkuse as main transcript	c.-141T>G	5_prime_UTR_variant	1/5	5		ENSP00000450339.1	P62854

Frequencies

GnomAD3 genomes

AF:

0.000880

AC:

134

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0244

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.00110

AC:

562

AN:

508738

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

290

AN XY:

270792

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000660

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0156

Gnomad4 SAS exome

AF:

0.000971

Gnomad4 FIN exome

AF:

0.0000925

Gnomad4 NFE exome

AF:

0.0000203

Gnomad4 OTH exome

AF:

0.000175

GnomAD4 genome

AF:

0.000873

AC:

133

AN:

152346

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0241

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.00117

Asia WGS

AF:

0.00462

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

-0.82

CADD

Benign

0.10

DANN

Benign

0.47

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

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