Genetic Variant RPN2:c.14-57C>A (chr20-37184123-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.504

Publications

5 publications found

Variant links:

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]

RPN2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 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 VariationId is 1275370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.532 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RPN2	NM_002951.5	MANE Select	c.14-57C>A	intron	N/A	NP_002942.2
RPN2	NM_001324301.2		c.14-57C>A	intron	N/A	NP_001311230.1
RPN2	NM_001324304.2		c.14-57C>A	intron	N/A	NP_001311233.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPN2	ENST00000237530.11	TSL:1 MANE Select	c.14-57C>A	intron	N/A	ENSP00000237530.6	P04844-1
RPN2	ENST00000705448.1		c.14-57C>A	intron	N/A	ENSP00000516126.1	A0A994J5J1
RPN2	ENST00000892636.1		c.14-57C>A	intron	N/A	ENSP00000562695.1

Frequencies

GnomAD3 genomes

AF:

0.379

AC:

57626

AN:

151862

Hom.:

11995

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.303

AC:

75859

AN:

250236

AF XY:

0.305

show subpopulations

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 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.:

AF XY:

0.334

AC XY:

240245

AN XY:

718718

show subpopulations

African (AFR)

AF:

0.539

AC:

17825

AN:

33042

American (AMR)

AF:

0.198

AC:

8835

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.370

AC:

9605

AN:

25990

East Asian (EAS)

AF:

0.00756

AC:

299

AN:

39570

South Asian (SAS)

AF:

0.263

AC:

22578

AN:

85688

European-Finnish (FIN)

AF:

0.319

AC:

17008

AN:

53350

Middle Eastern (MID)

AF:

0.410

AC:

2351

AN:

5728

European-Non Finnish (NFE)

AF:

0.353

AC:

386409

AN:

1094422

Other (OTH)

AF:

0.340

AC:

20260

AN:

59676

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

15180

30359

45539

60718

75898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12034

24068

36102

48136

60170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.379

AC:

57667

AN:

151980

Hom.:

12010

Cov.:

AF XY:

0.372

AC XY:

27619

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.537

AC:

22251

AN:

41400

American (AMR)

AF:

0.270

AC:

4124

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.369

AC:

1282

AN:

3470

East Asian (EAS)

AF:

0.00984

AC:

AN:

5182

South Asian (SAS)

AF:

0.251

AC:

1213

AN:

4824

European-Finnish (FIN)

AF:

0.314

AC:

3307

AN:

10548

Middle Eastern (MID)

AF:

0.442

AC:

129

AN:

292

European-Non Finnish (NFE)

AF:

0.357

AC:

24232

AN:

67956

Other (OTH)

AF:

0.383

AC:

809

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1749

3497

5246

6994

8743

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

544

1088

1632

2176

2720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.375

Hom.:

3330

Bravo

AF:

0.383

Asia WGS

AF:

0.166

AC:

579

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.4

(source)

DANN

Benign

0.62

PhyloP100

0.50

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over