rs4147645

Variant names:

• chr19-8321778-T-C
• rs4147645
• ENST00000602140.1:n.198T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000602140.1(RPS28):​n.198T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0501 in 1,520,664 control chromosomes in the GnomAD database, including 4,393 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1892 hom., cov: 32)
  • Exomes 𝑓: 0.043 (2501 hom.)
• Consequence: RPS28 ENST00000602140.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.16
• Publications: 6 publications found

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: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics
• Diamond-Blackfan anemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 19-8321778-T-C is Benign according to our data. Variant chr19-8321778-T-C is described in ClinVar as Benign. ClinVar VariationId is 1268375.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS28	NM_001031.5	c.87+75T>C		intron_variant	Intron 2 of 3	ENST00000600659.3	NP_001022.1
RPS28	XM_047439201.1	c.87+75T>C		intron_variant	Intron 2 of 2		XP_047295157.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS28	ENST00000602140.1	n.198T>C		non_coding_transcript_exon_variant	Exon 2 of 2	1
RPS28	ENST00000600659.3	c.87+75T>C		intron_variant	Intron 2 of 3	1	NM_001031.5	ENSP00000472469.1
RPS28	ENST00000449223.3	n.535T>C		non_coding_transcript_exon_variant	Exon 2 of 3	2
RPS28	ENST00000417088.2	n.70+75T>C		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16939 AN: 152086 Hom.: 1882 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0677

Gnomad ASJ AF: 0.0580

Gnomad EAS AF: 0.0889

Gnomad SAS AF: 0.0429

Gnomad FIN AF: 0.0297

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0346

Gnomad OTH AF: 0.103

GnomAD2 exomes AF: 0.0569 AC: 8505 AN: 149496 AF XY: 0.0536

Gnomad AFR exome AF: 0.300

Gnomad AMR exome AF: 0.0450

Gnomad ASJ exome AF: 0.0645

Gnomad EAS exome AF: 0.0899

Gnomad FIN exome AF: 0.0271

Gnomad NFE exome AF: 0.0363

Gnomad OTH exome AF: 0.0461

GnomAD4 exome AF: 0.0433 AC: 59199 AN: 1368460 Hom.: 2501 Cov.: 25 AF XY: 0.0423 AC XY: 28472 AN XY: 673798

African (AFR) AF: 0.300 AC: 9395 AN: 31340

American (AMR) AF: 0.0477 AC: 1688 AN: 35406

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 1438 AN: 23648

East Asian (EAS) AF: 0.0720 AC: 2619 AN: 36384

South Asian (SAS) AF: 0.0364 AC: 2790 AN: 76606

European-Finnish (FIN) AF: 0.0282 AC: 1328 AN: 47018

Middle Eastern (MID) AF: 0.0659 AC: 367 AN: 5566

European-Non Finnish (NFE) AF: 0.0343 AC: 36179 AN: 1055522

Other (OTH) AF: 0.0596 AC: 3395 AN: 56970

GnomAD4 genome AF: 0.112 AC: 16971 AN: 152204 Hom.: 1892 Cov.: 32 AF XY: 0.111 AC XY: 8240 AN XY: 74398

African (AFR) AF: 0.293 AC: 12147 AN: 41510

American (AMR) AF: 0.0676 AC: 1033 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0580 AC: 201 AN: 3468

East Asian (EAS) AF: 0.0891 AC: 461 AN: 5176

South Asian (SAS) AF: 0.0427 AC: 206 AN: 4826

European-Finnish (FIN) AF: 0.0297 AC: 315 AN: 10608

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0346 AC: 2354 AN: 68010

Other (OTH) AF: 0.101 AC: 213 AN: 2114

Alfa AF: 0.0697 Hom.: 249

Bravo AF: 0.123

Asia WGS AF: 0.0830 AC: 288 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 16, 2021

GeneDx

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	-0.73
CADD	Benign	3.7
DANN	Benign	0.81
PhyloP100		-1.2
PromoterAI		0.054	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs4147645; hg19: chr19-8386662;