chr2-55233615-C-T

Variant names:

• chr2-55233615-C-T
• rs6545480
• NM_002954.6:c.103+198C>T

Variant summary

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

The NM_002954.6(RPS27A):​c.103+198C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 601,414 control chromosomes in the GnomAD database, including 165,310 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.75 (43060 hom., cov: 31)
  • Exomes 𝑓: 0.74 (122250 hom.)
• Consequence: RPS27A NM_002954.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.978
• Publications: 16 publications found

Genes affected

RPS27A (HGNC:10417): (ribosomal protein S27a) Ubiquitin, a highly conserved protein that has a major role in targeting cellular proteins for degradation by the 26S proteosome, is synthesized as a precursor protein consisting of either polyubiquitin chains or a single ubiquitin fused to an unrelated protein. This gene encodes a fusion protein consisting of ubiquitin at the N terminus and ribosomal protein S27a at the C terminus. When expressed in yeast, the protein is post-translationally processed, generating free ubiquitin monomer and ribosomal protein S27a. Ribosomal protein S27a is a component of the 40S subunit of the ribosome and belongs to the S27AE family of ribosomal proteins. It contains C4-type zinc finger domains and is located in the cytoplasm. Pseudogenes derived from this gene are present in the genome. As with ribosomal protein S27a, ribosomal protein L40 is also synthesized as a fusion protein with ubiquitin; similarly, ribosomal protein S30 is synthesized as a fusion protein with the ubiquitin-like protein fubi. Multiple alternatively spliced transcript variants that encode the same proteins have been identified.[provided by RefSeq, Sep 2008]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 2-55233615-C-T is Benign according to our data. Variant chr2-55233615-C-T is described in ClinVar as Benign. ClinVar VariationId is 1246341.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002954.6. 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
	RPS27A	NM_002954.6	MANE Select	c.103+198C>T		intron	N/A	NP_002945.1	B2RDW1
	RPS27A	NM_001135592.2		c.103+198C>T		intron	N/A	NP_001129064.1	B2RDW1
	RPS27A	NM_001177413.1		c.103+198C>T		intron	N/A	NP_001170884.1	B2RDW1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS27A	ENST00000272317.11	TSL:1 MANE Select	c.103+198C>T		intron	N/A	ENSP00000272317.6	P62979
	RPS27A	ENST00000404735.1	TSL:1	c.103+198C>T		intron	N/A	ENSP00000385659.1	P62979
	RPS27A	ENST00000859841.1		c.103+198C>T		intron	N/A	ENSP00000529900.1

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114129 AN: 151964 Hom.: 43025 Cov.: 31

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.726

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.747

GnomAD4 exome AF: 0.735 AC: 330299 AN: 449332 Hom.: 122250 Cov.: 3 AF XY: 0.732 AC XY: 175562 AN XY: 239852

African (AFR) AF: 0.753 AC: 9366 AN: 12444

American (AMR) AF: 0.709 AC: 14568 AN: 20558

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 8935 AN: 13868

East Asian (EAS) AF: 0.619 AC: 18403 AN: 29724

South Asian (SAS) AF: 0.676 AC: 32192 AN: 47588

European-Finnish (FIN) AF: 0.835 AC: 24873 AN: 29784

Middle Eastern (MID) AF: 0.641 AC: 1239 AN: 1934

European-Non Finnish (NFE) AF: 0.754 AC: 202103 AN: 267932

Other (OTH) AF: 0.730 AC: 18620 AN: 25500

GnomAD4 genome AF: 0.751 AC: 114214 AN: 152082 Hom.: 43060 Cov.: 31 AF XY: 0.750 AC XY: 55783 AN XY: 74340

African (AFR) AF: 0.761 AC: 31574 AN: 41476

American (AMR) AF: 0.726 AC: 11102 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2203 AN: 3472

East Asian (EAS) AF: 0.641 AC: 3304 AN: 5158

South Asian (SAS) AF: 0.653 AC: 3144 AN: 4816

European-Finnish (FIN) AF: 0.842 AC: 8898 AN: 10568

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.757 AC: 51467 AN: 67994

Other (OTH) AF: 0.750 AC: 1584 AN: 2112

Alfa AF: 0.747 Hom.: 150298

Bravo AF: 0.745

Asia WGS AF: 0.668 AC: 2325 AN: 3478

ClinVar

ClinVar submissions

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	-0.88
CADD	Benign	0.28
DANN	Benign	0.72
PhyloP100		-0.98
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs6545480; hg19: chr2-55460751;