20-37181380-T-C

Variant names:

• chr20-37181380-T-C
• rs6031882
• NM_002951.5:c.13+2011T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002951.5(RPN2):​c.13+2011T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 151,388 control chromosomes in the GnomAD database, including 13,645 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (13645 hom., cov: 29)
• Consequence: RPN2 NM_002951.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 16 publications found

Genes affected

RPN2 (HGNC:10382): (ribophorin II) This gene encodes a type I integral membrane protein found only in the rough endoplasmic reticulum. The encoded protein is part of an N-oligosaccharyl transferase complex that links high mannose oligosaccharides to asparagine residues found in the Asn-X-Ser/Thr consensus motif of nascent polypeptide chains. This protein is similar in sequence to the yeast oligosaccharyl transferase subunit SWP1. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPN2	NM_002951.5	c.13+2011T>C		intron_variant	Intron 1 of 16	ENST00000237530.11	NP_002942.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPN2	ENST00000237530.11	c.13+2011T>C		intron_variant	Intron 1 of 16	1	NM_002951.5	ENSP00000237530.6

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61507 AN: 151272 Hom.: 13623 Cov.: 29

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.414

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

GnomAD4 genome AF: 0.407 AC: 61567 AN: 151388 Hom.: 13645 Cov.: 29 AF XY: 0.398 AC XY: 29402 AN XY: 73940

African (AFR) AF: 0.566 AC: 23313 AN: 41174

American (AMR) AF: 0.290 AC: 4418 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1473 AN: 3466

East Asian (EAS) AF: 0.00983 AC: 51 AN: 5188

South Asian (SAS) AF: 0.261 AC: 1254 AN: 4812

European-Finnish (FIN) AF: 0.332 AC: 3434 AN: 10336

Middle Eastern (MID) AF: 0.479 AC: 140 AN: 292

European-Non Finnish (NFE) AF: 0.388 AC: 26352 AN: 67884

Other (OTH) AF: 0.409 AC: 860 AN: 2102

Alfa AF: 0.379 Hom.: 39332

Bravo AF: 0.412

Asia WGS AF: 0.176 AC: 614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.49
PhyloP100		-1.2
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: rs6031882; hg19: chr20-35809783;