dbSNP rs2241590: RPS28:c.87+114G>A (chr19-8321817-G-A) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBA1

The NM_001031.5(RPS28):c.87+114G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 1,489,114 control chromosomes in the GnomAD database, including 113,789 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 17181 hom., cov: 32)

Exomes 𝑓: 0.37 ( 96608 hom. )

Consequence

RPS28
NM_001031.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.60

Publications

20 publications found

Variant links:

Genes affected

RPS28 (HGNC:10418): (ribosomal protein S28) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S28E family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

RPS28 Gene-Disease associations (from GenCC):

Diamond-Blackfan anemia 15 with mandibulofacial dysostosis
Inheritance: AD Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
Diamond-Blackfan anemia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

RPS28 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BP6

Variant 19-8321817-G-A is Benign according to our data. Variant chr19-8321817-G-A is described in ClinVar as Benign. ClinVar VariationId is 1181154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031.5. 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
	RPS28	NM_001031.5	MANE Select	c.87+114G>A		intron	N/A	NP_001022.1	P62857

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPS28	ENST00000600659.3	TSL:1 MANE Select	c.87+114G>A	intron	N/A	ENSP00000472469.1	P62857
RPS28	ENST00000602140.1	TSL:1	n.237G>A	non_coding_transcript_exon	Exon 2 of 2
RPS28	ENST00000930317.1		c.87+114G>A	intron	N/A	ENSP00000600376.1

Frequencies

GnomAD3 genomes

AF:

0.445

AC:

67575

AN:

151892

Hom.:

17134

Cov.:

show subpopulations

Gnomad AFR

AF:

0.700

Gnomad AMI

AF:

0.330

Gnomad AMR

AF:

0.304

Gnomad ASJ

AF:

0.312

Gnomad EAS

AF:

0.251

Gnomad SAS

AF:

0.455

Gnomad FIN

AF:

0.286

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.370

Gnomad OTH

AF:

0.406

GnomAD2 exomes

AF:

0.361

AC:

56763

AN:

157072

AF XY:

0.370

show subpopulations

Gnomad AFR exome

AF:

0.711

Gnomad AMR exome

AF:

0.243

Gnomad ASJ exome

AF:

0.330

Gnomad EAS exome

AF:

0.261

Gnomad FIN exome

AF:

0.271

Gnomad NFE exome

AF:

0.377

Gnomad OTH exome

AF:

0.350

GnomAD4 exome

AF:

0.372

AC:

497019

AN:

1337104

Hom.:

96608

Cov.:

AF XY:

0.373

AC XY:

246806

AN XY:

661192

show subpopulations

African (AFR)

AF:

0.712

AC:

21716

AN:

30484

American (AMR)

AF:

0.249

AC:

8891

AN:

35710

Ashkenazi Jewish (ASJ)

AF:

0.325

AC:

8019

AN:

24642

East Asian (EAS)

AF:

0.239

AC:

8534

AN:

35690

South Asian (SAS)

AF:

0.450

AC:

35242

AN:

78338

European-Finnish (FIN)

AF:

0.274

AC:

13066

AN:

47662

Middle Eastern (MID)

AF:

0.406

AC:

2270

AN:

5588

European-Non Finnish (NFE)

AF:

0.370

AC:

378109

AN:

1023014

Other (OTH)

AF:

0.378

AC:

21172

AN:

55976

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

16262

32524

48785

65047

81309

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12098

24196

36294

48392

60490

<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:

0.445

AC:

67669

AN:

152010

Hom.:

17181

Cov.:

AF XY:

0.441

AC XY:

32735

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.700

AC:

29057

AN:

41482

American (AMR)

AF:

0.304

AC:

4639

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.312

AC:

1082

AN:

3468

East Asian (EAS)

AF:

0.251

AC:

1291

AN:

5152

South Asian (SAS)

AF:

0.455

AC:

2197

AN:

4826

European-Finnish (FIN)

AF:

0.286

AC:

3014

AN:

10556

Middle Eastern (MID)

AF:

0.384

AC:

113

AN:

294

European-Non Finnish (NFE)

AF:

0.370

AC:

25114

AN:

67940

Other (OTH)

AF:

0.408

AC:

862

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1759

3518

5278

7037

8796

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

600

1200

1800

2400

3000

<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:

0.381

Hom.:

19035

Bravo

AF:

0.457

Asia WGS

AF:

0.382

AC:

1327

AN:

3478

ClinVar

ClinVar submissions

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

-0.76

CADD

Benign

0.95

(source)

DANN

Benign

0.72

PhyloP100

-2.6

PromoterAI

-0.067

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.61

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.61

Position offset: 2

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