Genetic Variant NM_001031.5:c.*16+23T>C (chr19-8322114-T-C) – 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 NM_001031.5(RPS28):c.*16+23T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 1,603,438 control chromosomes in the GnomAD database, including 43,153 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5631 hom., cov: 32)

Exomes 𝑓: 0.22 ( 37522 hom. )

Consequence

RPS28
NM_001031.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.606

Publications

14 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 19-8322114-T-C is Benign according to our data. Variant chr19-8322114-T-C is described in ClinVar as Benign. ClinVar VariationId is 1244664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 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.*16+23T>C		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.*16+23T>C	intron	N/A	ENSP00000472469.1	P62857
RPS28	ENST00000602140.1	TSL:1	n.534T>C	non_coding_transcript_exon	Exon 2 of 2
RPS28	ENST00000948366.1		c.*39T>C	3_prime_UTR	Exon 3 of 3	ENSP00000618425.1

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

40298

AN:

151848

Hom.:

5623

Cov.:

show subpopulations

Gnomad AFR

AF:

0.342

Gnomad AMI

AF:

0.241

Gnomad AMR

AF:

0.322

Gnomad ASJ

AF:

0.254

Gnomad EAS

AF:

0.306

Gnomad SAS

AF:

0.118

Gnomad FIN

AF:

0.212

Gnomad MID

AF:

0.261

Gnomad NFE

AF:

0.222

Gnomad OTH

AF:

0.294

GnomAD2 exomes

AF:

0.239

AC:

56921

AN:

238388

AF XY:

0.226

show subpopulations

Gnomad AFR exome

AF:

0.343

Gnomad AMR exome

AF:

0.345

Gnomad ASJ exome

AF:

0.256

Gnomad EAS exome

AF:

0.303

Gnomad FIN exome

AF:

0.216

Gnomad NFE exome

AF:

0.220

Gnomad OTH exome

AF:

0.248

GnomAD4 exome

AF:

0.223

AC:

323371

AN:

1451472

Hom.:

37522

Cov.:

AF XY:

0.218

AC XY:

157215

AN XY:

721000

show subpopulations

African (AFR)

AF:

0.341

AC:

11340

AN:

33230

American (AMR)

AF:

0.336

AC:

14700

AN:

43752

Ashkenazi Jewish (ASJ)

AF:

0.247

AC:

6337

AN:

25664

East Asian (EAS)

AF:

0.272

AC:

10729

AN:

39498

South Asian (SAS)

AF:

0.104

AC:

8891

AN:

85408

European-Finnish (FIN)

AF:

0.216

AC:

11342

AN:

52622

Middle Eastern (MID)

AF:

0.248

AC:

1419

AN:

5716

European-Non Finnish (NFE)

AF:

0.221

AC:

244460

AN:

1105708

Other (OTH)

AF:

0.236

AC:

14153

AN:

59874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

13194

26388

39581

52775

65969

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8582

17164

25746

34328

42910

<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:

0.265

AC:

40327

AN:

151966

Hom.:

5631

Cov.:

AF XY:

0.264

AC XY:

19625

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.342

AC:

14181

AN:

41428

American (AMR)

AF:

0.322

AC:

4911

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.254

AC:

881

AN:

3472

East Asian (EAS)

AF:

0.307

AC:

1584

AN:

5160

South Asian (SAS)

AF:

0.117

AC:

562

AN:

4818

European-Finnish (FIN)

AF:

0.212

AC:

2232

AN:

10552

Middle Eastern (MID)

AF:

0.260

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.222

AC:

15074

AN:

67970

Other (OTH)

AF:

0.290

AC:

608

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1488

2976

4463

5951

7439

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

394

788

1182

1576

1970

<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:

0.234

Hom.:

19336

Bravo

AF:

0.279

Asia WGS

AF:

0.236

AC:

822

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Diamond-Blackfan anemia 15 with mandibulofacial dysostosis (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.4

(source)

DANN

Benign

0.64

PhyloP100

-0.61

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)

0.010

Details are displayed if max score is > 0.2

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