rs1131017

Variant names:

• chr12-56042145-C-G
• rs1131017
• NM_001029.5:c.-22C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-56042145-C-G
• chr12-56042145-C-A
• chr12-56042145-C-T

Variant summary

Our verdict is Benign. The variant received -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 premature start codon gain 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_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.358
• Publications: 110 publications found

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 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia 10

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
• Diamond-Blackfan anemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001029.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS26	NM_001029.5	MANE Select	c.-22C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	NP_001020.2
	RPS26	NM_001029.5	MANE Select	c.-22C>G		5_prime_UTR	Exon 1 of 4	NP_001020.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS26	ENST00000646449.2	MANE Select	c.-22C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	ENSP00000496643.1	P62854
	RPS26	ENST00000356464.10	TSL:1	c.-22C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	ENSP00000348849.5	P62854
	RPS26	ENST00000646449.2	MANE Select	c.-22C>G		5_prime_UTR	Exon 1 of 4	ENSP00000496643.1	P62854

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

GnomAD2 exomes AF: 0.617 AC: 154991 AN: 251118 AF XY: 0.623

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 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

African (AFR) AF: 0.214 AC: 7166 AN: 33442

American (AMR) AF: 0.748 AC: 33456 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 15235 AN: 26124

East Asian (EAS) AF: 0.796 AC: 31584 AN: 39690

South Asian (SAS) AF: 0.699 AC: 60245 AN: 86224

European-Finnish (FIN) AF: 0.587 AC: 31336 AN: 53370

Middle Eastern (MID) AF: 0.692 AC: 3991 AN: 5768

European-Non Finnish (NFE) AF: 0.577 AC: 640782 AN: 1110426

Other (OTH) AF: 0.586 AC: 35354 AN: 60344

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

African (AFR) AF: 0.226 AC: 9358 AN: 41454

American (AMR) AF: 0.650 AC: 9908 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1978 AN: 3472

East Asian (EAS) AF: 0.780 AC: 4026 AN: 5162

South Asian (SAS) AF: 0.705 AC: 3398 AN: 4818

European-Finnish (FIN) AF: 0.599 AC: 6342 AN: 10582

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.590 AC: 40069 AN: 67960

Other (OTH) AF: 0.560 AC: 1179 AN: 2104

Alfa AF: 0.493 Hom.: 2792

Bravo AF: 0.497

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Diamond-Blackfan anemia 10 (4)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.4
DANN	Benign	0.58
PhyloP100		0.36
PromoterAI		-0.13	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1131017; hg19: chr12-56435929;