Genetic Variant RPS28:c.*68G>A (chr19-8322323-G-A) – 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.*68G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 664,032 control chromosomes in the GnomAD database, including 103,281 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 27582 hom., cov: 31)

Exomes 𝑓: 0.54 ( 75699 hom. )

Consequence

RPS28
NM_001031.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.416

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 19-8322323-G-A is Benign according to our data. Variant chr19-8322323-G-A is described in ClinVar as [Benign]. Clinvar id is 1252932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS28	NM_001031.5 link	c.*68G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000600659.3	NP_001022.1	P62857B2R4R9
RPS28	XM_047439201.1 link	c.*248G>A		downstream_gene_variant			XP_047295157.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RPS28	ENST00000600659.3 link	c.*68G>A	3_prime_UTR_variant	Exon 4 of 4	1	NM_001031.5	ENSP00000472469.1	P62857
RPS28	ENST00000602140.1 link	n.743G>A	non_coding_transcript_exon_variant	Exon 2 of 2	1
RPS28	ENST00000417088.2 link	n.261G>A	non_coding_transcript_exon_variant	Exon 3 of 3	2
RPS28	ENST00000449223.3 link	n.900G>A	non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.595

AC:

90348

AN:

151872

Hom.:

27544

Cov.:

show subpopulations

Gnomad AFR

AF:

0.736

Gnomad AMI

AF:

0.547

Gnomad AMR

AF:

0.557

Gnomad ASJ

AF:

0.507

Gnomad EAS

AF:

0.471

Gnomad SAS

AF:

0.531

Gnomad FIN

AF:

0.468

Gnomad MID

AF:

0.582

Gnomad NFE

AF:

0.556

Gnomad OTH

AF:

0.596

GnomAD3 exomes

AF:

0.543

AC:

72936

AN:

134418

Hom.:

19982

AF XY:

0.542

AC XY:

39573

AN XY:

73078

show subpopulations

Gnomad AFR exome

AF:

0.738

Gnomad AMR exome

AF:

0.536

Gnomad ASJ exome

AF:

0.518

Gnomad EAS exome

AF:

0.483

Gnomad SAS exome

AF:

0.514

Gnomad FIN exome

AF:

0.458

Gnomad NFE exome

AF:

0.560

Gnomad OTH exome

AF:

0.548

GnomAD4 exome

AF:

0.539

AC:

276167

AN:

512042

Hom.:

75699

Cov.:

AF XY:

0.537

AC XY:

149407

AN XY:

278154

show subpopulations

Gnomad4 AFR exome

AF:

0.728

Gnomad4 AMR exome

AF:

0.532

Gnomad4 ASJ exome

AF:

0.514

Gnomad4 EAS exome

AF:

0.436

Gnomad4 SAS exome

AF:

0.517

Gnomad4 FIN exome

AF:

0.462

Gnomad4 NFE exome

AF:

0.553

Gnomad4 OTH exome

AF:

0.554

GnomAD4 genome

AF:

0.595

AC:

90426

AN:

151990

Hom.:

27582

Cov.:

AF XY:

0.590

AC XY:

43863

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.736

Gnomad4 AMR

AF:

0.557

Gnomad4 ASJ

AF:

0.507

Gnomad4 EAS

AF:

0.472

Gnomad4 SAS

AF:

0.531

Gnomad4 FIN

AF:

0.468

Gnomad4 NFE

AF:

0.556

Gnomad4 OTH

AF:

0.592

Alfa

AF:

0.564

Hom.:

4485

Bravo

AF:

0.608

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.6

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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