20-37184123-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002951.5(RPN2):c.14-57C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 1,594,134 control chromosomes in the GnomAD database, including 98,121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (12010 hom., cov: 32)
  • Exomes 𝑓: 0.34 (86111 hom.)
• Consequence: RPN2 NM_002951.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.504

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 20-37184123-C-A is Benign according to our data. Variant chr20-37184123-C-A is described in ClinVar as [Benign]. Clinvar id is 1275370.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPN2	NM_002951.5	c.14-57C>A		intron_variant		ENST00000237530.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPN2	ENST00000237530.11	c.14-57C>A		intron_variant		1	NM_002951.5	P1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57626 AN: 151862 Hom.: 11995 Cov.: 32

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.388

GnomAD3 exomes AF: 0.303 AC: 75859 AN: 250236 Hom.: 13284 AF XY: 0.305 AC XY: 41305 AN XY: 135330

Gnomad AFR exome AF: 0.537

Gnomad AMR exome AF: 0.185

Gnomad ASJ exome AF: 0.371

Gnomad EAS exome AF: 0.00604

Gnomad SAS exome AF: 0.265

Gnomad FIN exome AF: 0.315

Gnomad NFE exome AF: 0.354

Gnomad OTH exome AF: 0.338

GnomAD4 exome AF: 0.336 AC: 485170 AN: 1442154 Hom.: 86111 Cov.: 27 AF XY: 0.334 AC XY: 240245 AN XY: 718718

Gnomad4 AFR exome AF: 0.539

Gnomad4 AMR exome AF: 0.198

Gnomad4 ASJ exome AF: 0.370

Gnomad4 EAS exome AF: 0.00756

Gnomad4 SAS exome AF: 0.263

Gnomad4 FIN exome AF: 0.319

Gnomad4 NFE exome AF: 0.353

Gnomad4 OTH exome AF: 0.340

GnomAD4 genome AF: 0.379 AC: 57667 AN: 151980 Hom.: 12010 Cov.: 32 AF XY: 0.372 AC XY: 27619 AN XY: 74308

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.00984

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.383

Alfa AF: 0.372 Hom.: 3223

Bravo AF: 0.383

Asia WGS AF: 0.166 AC: 579 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 05, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	3.4
Dann	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs16986470; hg19: chr20-35812526;