rs4608

Variant names:

• chr20-37236651-C-T
• rs4608
• NM_002951.5:c.1825C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-37236651-C-T
• chr20-37236651-C-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_002951.5(RPN2):​c.1825C>T​(p.Leu609Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 1,613,738 control chromosomes in the GnomAD database, including 500,576 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (45851 hom., cov: 33)
  • Exomes 𝑓: 0.79 (454725 hom.)
• Consequence: RPN2 NM_002951.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.401
• Publications: 30 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 20-37236651-C-T is Benign according to our data. Variant chr20-37236651-C-T is described in ClinVar as Benign. ClinVar VariationId is 683687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.401 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002951.5. 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
	RPN2	NM_002951.5	MANE Select	c.1825C>T	p.Leu609Leu	synonymous	Exon 16 of 17	NP_002942.2
	RPN2	NM_001324301.2		c.1873C>T	p.Leu625Leu	synonymous	Exon 17 of 19	NP_001311230.1
	RPN2	NM_001324304.2		c.1825C>T	p.Leu609Leu	synonymous	Exon 16 of 18	NP_001311233.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPN2	ENST00000237530.11	TSL:1 MANE Select	c.1825C>T	p.Leu609Leu	synonymous	Exon 16 of 17	ENSP00000237530.6	P04844-1
	RPN2	ENST00000705448.1		c.1825C>T	p.Leu609Leu	synonymous	Exon 16 of 18	ENSP00000516126.1	A0A994J5J1
	RPN2	ENST00000892636.1		c.1894C>T	p.Leu632Leu	synonymous	Exon 17 of 18	ENSP00000562695.1

Frequencies

GnomAD3 genomes AF: 0.772 AC: 117454 AN: 152054 Hom.: 45826 Cov.: 33

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.746

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.810

Gnomad OTH AF: 0.794

GnomAD2 exomes AF: 0.740 AC: 185920 AN: 251138 AF XY: 0.746

Gnomad AFR exome AF: 0.774

Gnomad AMR exome AF: 0.674

Gnomad ASJ exome AF: 0.840

Gnomad EAS exome AF: 0.474

Gnomad FIN exome AF: 0.664

Gnomad NFE exome AF: 0.803

Gnomad OTH exome AF: 0.788

GnomAD4 exome AF: 0.786 AC: 1149108 AN: 1461566 Hom.: 454725 Cov.: 44 AF XY: 0.785 AC XY: 571095 AN XY: 727102

African (AFR) AF: 0.777 AC: 26017 AN: 33478

American (AMR) AF: 0.685 AC: 30626 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.842 AC: 22011 AN: 26132

East Asian (EAS) AF: 0.533 AC: 21173 AN: 39698

South Asian (SAS) AF: 0.730 AC: 62963 AN: 86256

European-Finnish (FIN) AF: 0.672 AC: 35897 AN: 53400

Middle Eastern (MID) AF: 0.854 AC: 4926 AN: 5768

European-Non Finnish (NFE) AF: 0.808 AC: 898041 AN: 1111734

Other (OTH) AF: 0.786 AC: 47454 AN: 60388

GnomAD4 genome AF: 0.772 AC: 117528 AN: 152172 Hom.: 45851 Cov.: 33 AF XY: 0.765 AC XY: 56873 AN XY: 74370

African (AFR) AF: 0.776 AC: 32190 AN: 41506

American (AMR) AF: 0.767 AC: 11739 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.840 AC: 2918 AN: 3472

East Asian (EAS) AF: 0.488 AC: 2517 AN: 5158

South Asian (SAS) AF: 0.725 AC: 3498 AN: 4828

European-Finnish (FIN) AF: 0.656 AC: 6943 AN: 10578

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.810 AC: 55102 AN: 68016

Other (OTH) AF: 0.794 AC: 1676 AN: 2112

Alfa AF: 0.793 Hom.: 180633

Bravo AF: 0.779

Asia WGS AF: 0.655 AC: 2279 AN: 3478

EpiCase AF: 0.827

EpiControl AF: 0.821

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	7.7
DANN	Benign	0.66
PhyloP100		0.40
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: rs4608; hg19: chr20-35865054; COSMIC: COSV52905845;