rs2280401

chr19-49496752-G-Achr19-49496752-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001015.5(RPS11):c.15+281G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,040 control chromosomes in the GnomAD database, including 1,498 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1498 hom., cov: 31)
• Consequence: RPS11 NM_001015.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS11	NM_001015.5	c.15+281G>A		intron_variant		ENST00000270625.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS11	ENST00000270625.7	c.15+281G>A		intron_variant		1	NM_001015.5	P1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18700 AN: 151922 Hom.: 1498 Cov.: 31

Gnomad AFR AF: 0.0271

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.131

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.123 AC: 18708 AN: 152040 Hom.: 1498 Cov.: 31 AF XY: 0.126 AC XY: 9369 AN XY: 74310

Gnomad4 AFR AF: 0.0270

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.133

Alfa AF: 0.156 Hom.: 4562

Bravo AF: 0.113

Asia WGS AF: 0.157 AC: 546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	1.7
Dann	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs2280401; hg19: chr19-50000009;