dbSNP rs4147644: RPS28:c.*16+23T>C (chr19-8322114-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS28	NM_001031.5 link	c.*16+23T>C		intron_variant	Intron 3 of 3	ENST00000600659.3	NP_001022.1	P62857B2R4R9
RPS28	XM_047439201.1 link	c.*39T>C		downstream_gene_variant			XP_047295157.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RPS28	ENST00000600659.3 link	c.*16+23T>C	intron_variant	Intron 3 of 3	1	NM_001031.5	ENSP00000472469.1	P62857
RPS28	ENST00000602140.1 link	n.534T>C	non_coding_transcript_exon_variant	Exon 2 of 2	1
RPS28	ENST00000417088.2 link	n.209+23T>C	intron_variant	Intron 2 of 2	2
RPS28	ENST00000449223.3 link	n.848+23T>C	intron_variant	Intron 2 of 2	2

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

GnomAD3 exomes

AF:

0.239

AC:

56921

AN:

238388

Hom.:

7393

AF XY:

0.226

AC XY:

29365

AN XY:

130130

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 SAS exome

AF:

0.105

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

Gnomad4 AFR exome

AF:

0.341

Gnomad4 AMR exome

AF:

0.336

Gnomad4 ASJ exome

AF:

0.247

Gnomad4 EAS exome

AF:

0.272

Gnomad4 SAS exome

AF:

0.104

Gnomad4 FIN exome

AF:

0.216

Gnomad4 NFE exome

AF:

0.221

Gnomad4 OTH exome

AF:

0.236

GnomAD4 genome

AF:

0.265

AC:

40327

AN:

151966

Hom.:

5631

Cov.:

AF XY:

0.264

AC XY:

19625

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.342

Gnomad4 AMR

AF:

0.322

Gnomad4 ASJ

AF:

0.254

Gnomad4 EAS

AF:

0.307

Gnomad4 SAS

AF:

0.117

Gnomad4 FIN

AF:

0.212

Gnomad4 NFE

AF:

0.222

Gnomad4 OTH

AF:

0.290

Alfa

AF:

0.228

Hom.:

8669

Bravo

AF:

0.279

Asia WGS

AF:

0.236

AC:

822

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Diamond-Blackfan anemia 15 with mandibulofacial dysostosis

Benign:1

Nov 07, 2021

Genome-Nilou Lab

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

-0.83

CADD

Benign

5.4

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over