19-49497909-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001015.5(RPS11):c.224-8G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,614,014 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (4 hom.)
• Consequence: RPS11 NM_001015.5 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00006257
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.53

Genes affected

RPS11 (HGNC:10384): (ribosomal protein S11) 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 member of the S17P family of ribosomal proteins that is a component of the 40S subunit. This gene is co-transcribed with the small nucleolar RNA gene U35B, which is located in the third intron. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed throughout the genome. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 19-49497909-G-A is Benign according to our data. Variant chr19-49497909-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2672784.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 208 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS11	NM_001015.5	c.224-8G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000270625.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS11	ENST00000270625.7	c.224-8G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001015.5	P1

Frequencies

GnomAD3 genomes AF: 0.00137 AC: 208 AN: 152084 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00212

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00158 AC: 398 AN: 251424 Hom.: 1 AF XY: 0.00151 AC XY: 205 AN XY: 135898

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.00168

Gnomad ASJ exome AF: 0.00675

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.00213

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00191 AC: 2785 AN: 1461812 Hom.: 4 Cov.: 31 AF XY: 0.00189 AC XY: 1372 AN XY: 727220

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.00157

Gnomad4 ASJ exome AF: 0.00712

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.000412

Gnomad4 NFE exome AF: 0.00210

Gnomad4 OTH exome AF: 0.00245

GnomAD4 genome AF: 0.00137 AC: 208 AN: 152202 Hom.: 0 Cov.: 32 AF XY: 0.00125 AC XY: 93 AN XY: 74426

Gnomad4 AFR AF: 0.000241

Gnomad4 AMR AF: 0.00150

Gnomad4 ASJ AF: 0.00692

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00212

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00178 Hom.: 0

Bravo AF: 0.00133

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00185

EpiControl AF: 0.00213

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2023

RPS11: BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.35
Dann	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000063
dbscSNV1_RF	Benign	0.0080
SpliceAI score (max)		0.0		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: rs148723163; hg19: chr19-50001166;