12-56042136-C-G

Variant names:

• chr12-56042136-C-G
• rs17118262
• NM_001029.5:c.-31C>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.-31C>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 0.077 in 1,613,226 control chromosomes in the GnomAD database, including 5,170 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.071 (419 hom., cov: 32)
  • Exomes 𝑓: 0.078 (4751 hom.)
• Consequence: RPS26 NM_001029.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.191

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=-0.79).
• BP6: Variant 12-56042136-C-G is Benign according to our data. Variant chr12-56042136-C-G is described in ClinVar as [Benign]. Clinvar id is 309855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS26	NM_001029.5	c.-31C>G		5_prime_UTR_variant	Exon 1 of 4	ENST00000646449.2	NP_001020.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS26	ENST00000646449	c.-31C>G		5_prime_UTR_variant	Exon 1 of 4		NM_001029.5	ENSP00000496643.1
RPS26	ENST00000356464	c.-31C>G		5_prime_UTR_variant	Exon 2 of 5	1		ENSP00000348849.5
RPS26	ENST00000552361	c.-31C>G		5_prime_UTR_variant	Exon 2 of 5	5		ENSP00000450339.1
RPS26	ENST00000548590.1	n.-4C>G		upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.0707 AC: 10751 AN: 152134 Hom.: 419 Cov.: 32

Gnomad AFR AF: 0.0645

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.0515

Gnomad ASJ AF: 0.0740

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.0532

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0806

Gnomad OTH AF: 0.0592

GnomAD3 exomes AF: 0.0660 AC: 16586 AN: 251222 Hom.: 629 AF XY: 0.0672 AC XY: 9124 AN XY: 135826

Gnomad AFR exome AF: 0.0665

Gnomad AMR exome AF: 0.0358

Gnomad ASJ exome AF: 0.0723

Gnomad EAS exome AF: 0.000598

Gnomad SAS exome AF: 0.0541

Gnomad FIN exome AF: 0.100

Gnomad NFE exome AF: 0.0813

Gnomad OTH exome AF: 0.0766

GnomAD4 exome AF: 0.0777 AC: 113456 AN: 1460974 Hom.: 4751 Cov.: 29 AF XY: 0.0771 AC XY: 56013 AN XY: 726854

Gnomad4 AFR exome AF: 0.0675

Gnomad4 AMR exome AF: 0.0384

Gnomad4 ASJ exome AF: 0.0716

Gnomad4 EAS exome AF: 0.000252

Gnomad4 SAS exome AF: 0.0544

Gnomad4 FIN exome AF: 0.0995

Gnomad4 NFE exome AF: 0.0836

Gnomad4 OTH exome AF: 0.0724

GnomAD4 genome AF: 0.0707 AC: 10757 AN: 152252 Hom.: 419 Cov.: 32 AF XY: 0.0710 AC XY: 5286 AN XY: 74440

Gnomad4 AFR AF: 0.0645

Gnomad4 AMR AF: 0.0514

Gnomad4 ASJ AF: 0.0740

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.0533

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.0806

Gnomad4 OTH AF: 0.0581

Alfa AF: 0.0467 Hom.: 52

Bravo AF: 0.0664

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Apr 24, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.2
DANN	Benign	0.53
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

Other links and lift over

dbSNP: rs17118262; hg19: chr12-56435920; COSMIC: COSV56267857; COSMIC: COSV56267857;