chr19-8321778-T-C

Position:

• chr19-8321778-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001031.5(RPS28):​c.87+75T>C variant causes a intron 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 NM_001031.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.16

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
RPS28	NM_001031.5	c.87+75T>C		intron_variant		ENST00000600659.3
RPS28	XM_047439201.1	c.87+75T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS28	ENST00000600659.3	c.87+75T>C		intron_variant		1	NM_001031.5	P1
RPS28	ENST00000602140.1	n.198T>C		non_coding_transcript_exon_variant	2/2	1
RPS28	ENST00000449223.3	n.535T>C		non_coding_transcript_exon_variant	2/3	2
RPS28	ENST00000417088.2	n.70+75T>C		intron_variant, non_coding_transcript_variant		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

GnomAD3 exomes AF: 0.0569 AC: 8505 AN: 149496 Hom.: 496 AF XY: 0.0536 AC XY: 4284 AN XY: 79958

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 SAS exome AF: 0.0381

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

Gnomad4 AFR exome AF: 0.300

Gnomad4 AMR exome AF: 0.0477

Gnomad4 ASJ exome AF: 0.0608

Gnomad4 EAS exome AF: 0.0720

Gnomad4 SAS exome AF: 0.0364

Gnomad4 FIN exome AF: 0.0282

Gnomad4 NFE exome AF: 0.0343

Gnomad4 OTH exome AF: 0.0596

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

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.0676

Gnomad4 ASJ AF: 0.0580

Gnomad4 EAS AF: 0.0891

Gnomad4 SAS AF: 0.0427

Gnomad4 FIN AF: 0.0297

Gnomad4 NFE AF: 0.0346

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0660 Hom.: 213

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.7
DANN	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs4147645; hg19: chr19-8386662;