rs2976050

Variant names:

• chr8-56069456-A-G
• rs2976050
• NM_001146227.3:c.*35+247T>C

Your query was ambiguous. Multiple possible variants found:

• chr8-56069456-A-G
• chr8-56069456-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001146227.3(RPS20):​c.*35+247T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 151,780 control chromosomes in the GnomAD database, including 5,994 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.27 (5994 hom., cov: 31)
• Consequence: RPS20 NM_001146227.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.502
• Publications: 2 publications found

Genes affected

RPS20 (HGNC:10405): (ribosomal protein S20) 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 S10P family of ribosomal proteins. It is located in the cytoplasm. This gene is co-transcribed with the small nucleolar RNA gene U54, which is located in its second intron. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Two transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Apr 2009]

RPS20 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia

  Inheritance: AD Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: PanelApp Australia, Orphanet, Ambry Genetics
• familial colorectal cancer

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• familial colorectal cancer type X

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary nonpolyposis colon cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• Lynch syndrome

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 8-56069456-A-G is Benign according to our data. Variant chr8-56069456-A-G is described in ClinVar as Benign. ClinVar VariationId is 1223975.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146227.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS20	NM_001146227.3		c.*35+247T>C		intron	N/A	NP_001139699.1	P60866-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS20	ENST00000519807.5	TSL:2	c.*35+247T>C		intron	N/A	ENSP00000429374.1	P60866-2
	RPS20	ENST00000618656.2	TSL:3	c.*35+247T>C		intron	N/A	ENSP00000478703.2	A0A7P0S5H5
	RPS20	ENST00000676461.1		n.*2547+1087T>C		intron	N/A	ENSP00000504670.1	P60866-1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41093 AN: 151662 Hom.: 5990 Cov.: 31

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.0239

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.271 AC: 41131 AN: 151780 Hom.: 5994 Cov.: 31 AF XY: 0.263 AC XY: 19488 AN XY: 74170

African (AFR) AF: 0.348 AC: 14396 AN: 41370

American (AMR) AF: 0.253 AC: 3856 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1228 AN: 3468

East Asian (EAS) AF: 0.0240 AC: 123 AN: 5132

South Asian (SAS) AF: 0.130 AC: 625 AN: 4804

European-Finnish (FIN) AF: 0.182 AC: 1922 AN: 10552

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17869 AN: 67898

Other (OTH) AF: 0.285 AC: 602 AN: 2110

Alfa AF: 0.256 Hom.: 701

Bravo AF: 0.282

Asia WGS AF: 0.0970 AC: 338 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.27
DANN	Benign	0.32
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2976050; hg19: chr8-56982015;