chr19-49496752-G-A

Variant names:

• chr19-49496752-G-A
• rs2280401
• NM_001015.5:c.15+281G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 43 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001015.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS11	NM_001015.5	MANE Select	c.15+281G>A		intron	N/A	NP_001006.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS11	ENST00000270625.7	TSL:1 MANE Select	c.15+281G>A		intron	N/A	ENSP00000270625.1
	RPS11	ENST00000596873.1	TSL:2	c.15+281G>A		intron	N/A	ENSP00000470447.1
	RPS11	ENST00000599561.1	TSL:5	c.15+281G>A		intron	N/A	ENSP00000471874.1

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

African (AFR) AF: 0.0270 AC: 1121 AN: 41506

American (AMR) AF: 0.109 AC: 1659 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 720 AN: 3466

East Asian (EAS) AF: 0.210 AC: 1081 AN: 5158

South Asian (SAS) AF: 0.149 AC: 718 AN: 4822

European-Finnish (FIN) AF: 0.191 AC: 2021 AN: 10576

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10943 AN: 67948

Other (OTH) AF: 0.133 AC: 279 AN: 2104

Alfa AF: 0.149 Hom.: 8682

Bravo AF: 0.113

Asia WGS AF: 0.157 AC: 546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.7
DANN	Benign	0.67
PhyloP100		-0.046
PromoterAI		0.0084	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2280401; hg19: chr19-50000009;