12-56042145-C-G

Position:

• chr12-56042145-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001029.5(RPS26):​c.-22C>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 0.581 in 1,612,112 control chromosomes in the GnomAD database, including 280,041 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (21890 hom., cov: 32)
  • Exomes 𝑓: 0.59 (258151 hom.)
• Consequence: RPS26 NM_001029.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.358

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 12-56042145-C-G is Benign according to our data. Variant chr12-56042145-C-G is described in ClinVar as [Benign]. Clinvar id is 309857.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS26	NM_001029.5	c.-22C>G		5_prime_UTR_variant	1/4	ENST00000646449.2	NP_001020.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS26	ENST00000646449.2	c.-22C>G		5_prime_UTR_variant	1/4		NM_001029.5	ENSP00000496643	P1
RPS26	ENST00000356464.10	c.-22C>G		5_prime_UTR_variant	2/5	1		ENSP00000348849	P1
RPS26	ENST00000552361.1	c.-22C>G		5_prime_UTR_variant	2/5	5		ENSP00000450339	P1
RPS26	ENST00000548590.1	n.6C>G		non_coding_transcript_exon_variant	1/3	5

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76819 AN: 151888 Hom.: 21887 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.560

GnomAD3 exomes AF: 0.617 AC: 154991 AN: 251118 Hom.: 50082 AF XY: 0.623 AC XY: 84554 AN XY: 135744

Gnomad AFR exome AF: 0.216

Gnomad AMR exome AF: 0.762

Gnomad ASJ exome AF: 0.588

Gnomad EAS exome AF: 0.790

Gnomad SAS exome AF: 0.700

Gnomad FIN exome AF: 0.599

Gnomad NFE exome AF: 0.586

Gnomad OTH exome AF: 0.617

GnomAD4 exome AF: 0.588 AC: 859149 AN: 1460106 Hom.: 258151 Cov.: 43 AF XY: 0.593 AC XY: 430778 AN XY: 726448

Gnomad4 AFR exome AF: 0.214

Gnomad4 AMR exome AF: 0.748

Gnomad4 ASJ exome AF: 0.583

Gnomad4 EAS exome AF: 0.796

Gnomad4 SAS exome AF: 0.699

Gnomad4 FIN exome AF: 0.587

Gnomad4 NFE exome AF: 0.577

Gnomad4 OTH exome AF: 0.586

GnomAD4 genome AF: 0.505 AC: 76834 AN: 152006 Hom.: 21890 Cov.: 32 AF XY: 0.515 AC XY: 38265 AN XY: 74304

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.650

Gnomad4 ASJ AF: 0.570

Gnomad4 EAS AF: 0.780

Gnomad4 SAS AF: 0.705

Gnomad4 FIN AF: 0.599

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.560

Alfa AF: 0.493 Hom.: 2792

Bravo AF: 0.497

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Diamond-Blackfan anemia 10 Benign:4

Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Dec 27, 2021	- -
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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 18, 2023	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 06, 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. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.4
DANN	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs1131017; hg19: chr12-56435929;