chr12-56042136-C-G

Variant names:

• chr12-56042136-C-G
• rs17118262
• NM_001029.5:c.-31C>G

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.-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
• Publications: 11 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=-0.79).
• BP6: Variant 12-56042136-C-G is Benign according to our data. Variant chr12-56042136-C-G is described in ClinVar as Benign. ClinVar VariationId 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.

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.-31C>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.-31C>G		5_prime_UTR	Exon 1 of 4	ENSP00000496643.1	P62854
	RPS26	ENST00000356464.10	TSL:1	c.-31C>G		5_prime_UTR	Exon 2 of 5	ENSP00000348849.5	P62854
	RPS26	ENST00000552361.1	TSL:5	c.-31C>G		5_prime_UTR	Exon 2 of 5	ENSP00000450339.1	P62854

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

GnomAD2 exomes AF: 0.0660 AC: 16586 AN: 251222 AF XY: 0.0672

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 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

African (AFR) AF: 0.0675 AC: 2258 AN: 33472

American (AMR) AF: 0.0384 AC: 1717 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0716 AC: 1870 AN: 26128

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39696

South Asian (SAS) AF: 0.0544 AC: 4692 AN: 86230

European-Finnish (FIN) AF: 0.0995 AC: 5311 AN: 53396

Middle Eastern (MID) AF: 0.0629 AC: 363 AN: 5768

European-Non Finnish (NFE) AF: 0.0836 AC: 92866 AN: 1111188

Other (OTH) AF: 0.0724 AC: 4369 AN: 60380

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

African (AFR) AF: 0.0645 AC: 2678 AN: 41540

American (AMR) AF: 0.0514 AC: 786 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0740 AC: 257 AN: 3472

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5176

South Asian (SAS) AF: 0.0533 AC: 257 AN: 4826

European-Finnish (FIN) AF: 0.100 AC: 1065 AN: 10600

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0806 AC: 5484 AN: 68022

Other (OTH) AF: 0.0581 AC: 123 AN: 2116

Alfa AF: 0.0467 Hom.: 52

Bravo AF: 0.0664

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.2
DANN	Benign	0.53
PhyloP100		0.19
PromoterAI		0.054	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs17118262; hg19: chr12-56435920; COSMIC: COSV56267857; COSMIC: COSV56267857;