chr8-56069724-G-A

Variant names:

• chr8-56069724-G-A
• rs78022071
• NM_001146227.3:c.*14C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001146227.3(RPS20):​c.*14C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,550,878 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (26 hom.)
• Consequence: RPS20 NM_001146227.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0230
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 8-56069724-G-A is Benign according to our data. Variant chr8-56069724-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1321491.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00189 (288/152180) while in subpopulation EAS AF = 0.047 (243/5172). AF 95% confidence interval is 0.0421. There are 3 homozygotes in GnomAd4. There are 164 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 288 AD gene.

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.*14C>T		3_prime_UTR	Exon 5 of 6	NP_001139699.1	P60866-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS20	ENST00000519807.5	TSL:2	c.*14C>T		3_prime_UTR	Exon 5 of 6	ENSP00000429374.1	P60866-2
	RPS20	ENST00000618656.2	TSL:3	c.*14C>T		3_prime_UTR	Exon 4 of 5	ENSP00000478703.2	A0A7P0S5H5
	RPS20	ENST00000676918.1		n.*3366C>T		non_coding_transcript_exon	Exon 4 of 5	ENSP00000503327.1	P60866-1

Frequencies

GnomAD3 genomes AF: 0.00189 AC: 288 AN: 152062 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0469

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00362 AC: 557 AN: 154024 AF XY: 0.00355

Gnomad AFR exome AF: 0.000758

Gnomad AMR exome AF: 0.000162

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0469

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000184

Gnomad OTH exome AF: 0.00231

GnomAD4 exome AF: 0.00104 AC: 1456 AN: 1398698 Hom.: 26 Cov.: 30 AF XY: 0.00104 AC XY: 718 AN XY: 689916

African (AFR) AF: 0.000285 AC: 9 AN: 31570

American (AMR) AF: 0.000168 AC: 6 AN: 35672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25172

East Asian (EAS) AF: 0.0331 AC: 1181 AN: 35690

South Asian (SAS) AF: 0.000593 AC: 47 AN: 79204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49268

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5698

European-Non Finnish (NFE) AF: 0.0000649 AC: 70 AN: 1078442

Other (OTH) AF: 0.00245 AC: 142 AN: 57982

GnomAD4 genome AF: 0.00189 AC: 288 AN: 152180 Hom.: 3 Cov.: 32 AF XY: 0.00220 AC XY: 164 AN XY: 74398

African (AFR) AF: 0.000554 AC: 23 AN: 41534

American (AMR) AF: 0.000196 AC: 3 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0470 AC: 243 AN: 5172

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 67986

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.000134 Hom.: 0

Bravo AF: 0.00254

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Lynch syndrome (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.48
PhyloP100		-0.023
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs78022071; hg19: chr8-56982283;