ENST00000356464.10:c.-356-183G>A

Variant names:

• chr12-56041628-G-A
• rs705704
• ENST00000356464.10:c.-356-183G>A

Variant summary

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

The ENST00000356464.10(RPS26):​c.-356-183G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 173,556 control chromosomes in the GnomAD database, including 6,851 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5525 hom., cov: 29)
  • Exomes 𝑓: 0.31 (1326 hom.)
• Consequence: RPS26 ENST00000356464.10 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0430

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]

ENSG00000257449 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 12-56041628-G-A is Benign according to our data. Variant chr12-56041628-G-A is described in ClinVar as [Benign]. Clinvar id is 1259753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS26	ENST00000356464.10	c.-356-183G>A		intron_variant	Intron 1 of 4	1		ENSP00000348849.5
ENSG00000257449	ENST00000551846.1	n.179C>T		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.260 AC: 38752 AN: 149122 Hom.: 5524 Cov.: 29

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.275

GnomAD4 exome AF: 0.310 AC: 7544 AN: 24328 Hom.: 1326 Cov.: 0 AF XY: 0.310 AC XY: 3988 AN XY: 12868

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.219

Gnomad4 ASJ exome AF: 0.377

Gnomad4 EAS exome AF: 0.230

Gnomad4 SAS exome AF: 0.270

Gnomad4 FIN exome AF: 0.354

Gnomad4 NFE exome AF: 0.362

Gnomad4 OTH exome AF: 0.334

GnomAD4 genome AF: 0.260 AC: 38749 AN: 149228 Hom.: 5525 Cov.: 29 AF XY: 0.256 AC XY: 18675 AN XY: 72810

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.336

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.273

Alfa AF: 0.308 Hom.: 7453

Bravo AF: 0.247

Asia WGS AF: 0.180 AC: 629 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.3
DANN	Benign	0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs705704; hg19: chr12-56435412;