Genetic Variant RPS26:c.-356-183G>A (chr12-56041628-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0430

Publications

61 publications found

Variant links:

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: G2P, Labcorp Genetics (formerly Invitae)
Diamond-Blackfan anemia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

RPS26 links:

ENSG00000257449 (HGNC:):

ENSG00000257449 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000356464.10. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RPS26	ENST00000356464.10	TSL:1	c.-356-183G>A	intron	N/A	ENSP00000348849.5
ENSG00000257449	ENST00000551846.1	TSL:3	n.179C>T	non_coding_transcript_exon	Exon 1 of 2
RPS26	ENST00000925486.1		c.-539G>A	upstream_gene	N/A	ENSP00000595545.1

Frequencies

GnomAD3 genomes

AF:

0.260

AC:

38752

AN:

149122

Hom.:

5524

Cov.:

show subpopulations

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.:

AF XY:

0.310

AC XY:

3988

AN XY:

12868

show subpopulations

African (AFR)

AF:

0.110

AC:

AN:

842

American (AMR)

AF:

0.219

AC:

659

AN:

3008

Ashkenazi Jewish (ASJ)

AF:

0.377

AC:

104

AN:

276

East Asian (EAS)

AF:

0.230

AC:

399

AN:

1732

South Asian (SAS)

AF:

0.270

AC:

1048

AN:

3886

European-Finnish (FIN)

AF:

0.354

AC:

201

AN:

568

Middle Eastern (MID)

AF:

0.340

AC:

AN:

European-Non Finnish (NFE)

AF:

0.362

AC:

4671

AN:

12912

Other (OTH)

AF:

0.334

AC:

352

AN:

1054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.543

Heterozygous variant carriers

242

484

725

967

1209

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

216

288

360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.260

AC:

38749

AN:

149228

Hom.:

5525

Cov.:

AF XY:

0.256

AC XY:

18675

AN XY:

72810

show subpopulations

African (AFR)

AF:

0.135

AC:

5500

AN:

40706

American (AMR)

AF:

0.230

AC:

3427

AN:

14926

Ashkenazi Jewish (ASJ)

AF:

0.336

AC:

1155

AN:

3440

East Asian (EAS)

AF:

0.219

AC:

1077

AN:

4908

South Asian (SAS)

AF:

0.246

AC:

1146

AN:

4662

European-Finnish (FIN)

AF:

0.313

AC:

3149

AN:

10060

Middle Eastern (MID)

AF:

0.252

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.330

AC:

22207

AN:

67244

Other (OTH)

AF:

0.273

AC:

571

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1408

2817

4225

5634

7042

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

408

816

1224

1632

2040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.298

Hom.:

9271

Bravo

AF:

0.247

Asia WGS

AF:

0.180

AC:

629

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.3

(source)

DANN

Benign

0.79

PhyloP100

0.043

PromoterAI

0.016

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over