rs6737227

Variant names:

• chr2-55233469-A-T
• rs6737227
• NM_002954.6:c.103+52A>T

Your query was ambiguous. Multiple possible variants found:

• chr2-55233469-A-T
• chr2-55233469-A-G

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+52A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 1,341,404 control chromosomes in the GnomAD database, including 387,529 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (44256 hom., cov: 32)
  • Exomes 𝑓: 0.76 (343273 hom.)
• Consequence: RPS27A NM_002954.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.63
• Publications: 10 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 2-55233469-A-T is Benign according to our data. Variant chr2-55233469-A-T is described in ClinVar as Benign. ClinVar VariationId is 1238560.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.768 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+52A>T		intron	N/A	NP_002945.1	B2RDW1
	RPS27A	NM_001135592.2		c.103+52A>T		intron	N/A	NP_001129064.1	B2RDW1
	RPS27A	NM_001177413.1		c.103+52A>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+52A>T		intron	N/A	ENSP00000272317.6	P62979
	RPS27A	ENST00000404735.1	TSL:1	c.103+52A>T		intron	N/A	ENSP00000385659.1	P62979
	RPS27A	ENST00000859841.1		c.103+52A>T		intron	N/A	ENSP00000529900.1

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115713 AN: 151954 Hom.: 44220 Cov.: 32

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.862

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.844

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.760

GnomAD2 exomes AF: 0.741 AC: 178080 AN: 240220 AF XY: 0.740

Gnomad AFR exome AF: 0.764

Gnomad AMR exome AF: 0.714

Gnomad ASJ exome AF: 0.666

Gnomad EAS exome AF: 0.642

Gnomad FIN exome AF: 0.841

Gnomad NFE exome AF: 0.767

Gnomad OTH exome AF: 0.741

GnomAD4 exome AF: 0.758 AC: 902075 AN: 1189332 Hom.: 343273 Cov.: 16 AF XY: 0.757 AC XY: 457708 AN XY: 604954

African (AFR) AF: 0.761 AC: 21245 AN: 27930

American (AMR) AF: 0.717 AC: 31249 AN: 43580

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 16157 AN: 24372

East Asian (EAS) AF: 0.618 AC: 23584 AN: 38168

South Asian (SAS) AF: 0.683 AC: 54678 AN: 80088

European-Finnish (FIN) AF: 0.840 AC: 44552 AN: 53018

Middle Eastern (MID) AF: 0.671 AC: 2548 AN: 3800

European-Non Finnish (NFE) AF: 0.773 AC: 669895 AN: 867124

Other (OTH) AF: 0.745 AC: 38167 AN: 51252

GnomAD4 genome AF: 0.761 AC: 115800 AN: 152072 Hom.: 44256 Cov.: 32 AF XY: 0.761 AC XY: 56552 AN XY: 74322

African (AFR) AF: 0.765 AC: 31693 AN: 41444

American (AMR) AF: 0.741 AC: 11331 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 2272 AN: 3470

East Asian (EAS) AF: 0.627 AC: 3245 AN: 5172

South Asian (SAS) AF: 0.658 AC: 3170 AN: 4818

European-Finnish (FIN) AF: 0.844 AC: 8934 AN: 10580

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.773 AC: 52568 AN: 67990

Other (OTH) AF: 0.763 AC: 1609 AN: 2110

Alfa AF: 0.724 Hom.: 4498

Bravo AF: 0.756

Asia WGS AF: 0.667 AC: 2320 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	0.30
DANN	Benign	0.41
PhyloP100		-3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs6737227; hg19: chr2-55460605;