20-37184123-C-A

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

2

Clinical Significance

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

Conservation

PhyloP100: 0.504
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]

Genome browser will be placed here

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 id 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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RPN2NM_002951.5 linkc.14-57C>A intron_variant Intron 1 of 16 ENST00000237530.11 NP_002942.2 P04844-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RPN2ENST00000237530.11 linkc.14-57C>A intron_variant Intron 1 of 16 1 NM_002951.5 ENSP00000237530.6 P04844-1

Frequencies

GnomAD3 genomes
AF:
0.379
AC:
57626
AN:
151862
Hom.:
11995
Cov.:
32
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.:
27
AF XY:
0.334
AC XY:
240245
AN XY:
718718
show subpopulations
Gnomad4 AFR exome
AF:
0.539
AC:
17825
AN:
33042
Gnomad4 AMR exome
AF:
0.198
AC:
8835
AN:
44688
Gnomad4 ASJ exome
AF:
0.370
AC:
9605
AN:
25990
Gnomad4 EAS exome
AF:
0.00756
AC:
299
AN:
39570
Gnomad4 SAS exome
AF:
0.263
AC:
22578
AN:
85688
Gnomad4 FIN exome
AF:
0.319
AC:
17008
AN:
53350
Gnomad4 NFE exome
AF:
0.353
AC:
386409
AN:
1094422
Gnomad4 Remaining exome
AF:
0.340
AC:
20260
AN:
59676
Heterozygous variant carriers
0
15180
30359
45539
60718
75898
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
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.:
32
AF XY:
0.372
AC XY:
27619
AN XY:
74308
show subpopulations
Gnomad4 AFR
AF:
0.537
AC:
0.537464
AN:
0.537464
Gnomad4 AMR
AF:
0.270
AC:
0.269719
AN:
0.269719
Gnomad4 ASJ
AF:
0.369
AC:
0.369452
AN:
0.369452
Gnomad4 EAS
AF:
0.00984
AC:
0.00984176
AN:
0.00984176
Gnomad4 SAS
AF:
0.251
AC:
0.251451
AN:
0.251451
Gnomad4 FIN
AF:
0.314
AC:
0.313519
AN:
0.313519
Gnomad4 NFE
AF:
0.357
AC:
0.356584
AN:
0.356584
Gnomad4 OTH
AF:
0.383
AC:
0.383412
AN:
0.383412
Heterozygous variant carriers
0
1749
3497
5246
6994
8743
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
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

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Sep 05, 2018
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
3.4
DANN
Benign
0.62
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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs16986470; hg19: chr20-35812526; API