rs116472667

Variant names:

• chr8-56072854-C-G
• rs116472667
• NM_001146227.3:c.333+263G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-56072854-C-G
• chr8-56072854-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001146227.3(RPS20):​c.333+263G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00571 in 1,220,546 control chromosomes in the GnomAD database, including 153 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (80 hom., cov: 32)
  • Exomes 𝑓: 0.0037 (73 hom.)
• Consequence: RPS20 NM_001146227.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.754
• Publications: 0 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):

• familial colorectal cancer

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• Diamond-Blackfan anemia

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 8-56072854-C-G is Benign according to our data. Variant chr8-56072854-C-G is described in ClinVar as Benign. ClinVar VariationId is 1278075.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0583 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.333+263G>C		intron	N/A	NP_001139699.1	P60866-2
	RPS20	NM_001023.4	MANE Select	c.*236G>C		downstream_gene	N/A	NP_001014.1	P60866-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS20	ENST00000519807.5	TSL:2	c.333+263G>C		intron	N/A	ENSP00000429374.1	P60866-2
	RPS20	ENST00000618656.2	TSL:3	c.315+263G>C		intron	N/A	ENSP00000478703.2	A0A7P0S5H5
	RPS20	ENST00000676461.1		n.*236G>C		non_coding_transcript_exon	Exon 4 of 5	ENSP00000504670.1	P60866-1

Frequencies

GnomAD3 genomes AF: 0.0194 AC: 2953 AN: 152064 Hom.: 78 Cov.: 32

Gnomad AFR AF: 0.0602

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.0181

Gnomad SAS AF: 0.00662

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00191

Gnomad OTH AF: 0.0196

GnomAD4 exome AF: 0.00375 AC: 4004 AN: 1068364 Hom.: 73 Cov.: 27 AF XY: 0.00373 AC XY: 1895 AN XY: 507570

African (AFR) AF: 0.0640 AC: 1558 AN: 24362

American (AMR) AF: 0.00634 AC: 74 AN: 11678

Ashkenazi Jewish (ASJ) AF: 0.00355 AC: 45 AN: 12664

East Asian (EAS) AF: 0.0201 AC: 432 AN: 21532

South Asian (SAS) AF: 0.00547 AC: 206 AN: 37642

European-Finnish (FIN) AF: 0.000158 AC: 2 AN: 12662

Middle Eastern (MID) AF: 0.0138 AC: 36 AN: 2600

European-Non Finnish (NFE) AF: 0.00153 AC: 1379 AN: 903724

Other (OTH) AF: 0.00655 AC: 272 AN: 41500

GnomAD4 genome AF: 0.0195 AC: 2962 AN: 152182 Hom.: 80 Cov.: 32 AF XY: 0.0192 AC XY: 1432 AN XY: 74398

African (AFR) AF: 0.0603 AC: 2503 AN: 41510

American (AMR) AF: 0.0100 AC: 153 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3472

East Asian (EAS) AF: 0.0181 AC: 94 AN: 5184

South Asian (SAS) AF: 0.00621 AC: 30 AN: 4830

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10588

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00191 AC: 130 AN: 68008

Other (OTH) AF: 0.0194 AC: 41 AN: 2112

Alfa AF: 0.0127 Hom.: 4

Bravo AF: 0.0222

Asia WGS AF: 0.0130 AC: 46 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.49
PhyloP100		-0.75
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: rs116472667; hg19: chr8-56985413;