rs34781001
Positions:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_002950.4(RPN1):c.1647C>T(p.Ser549=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00235 in 1,612,680 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.013 ( 40 hom., cov: 32)
Exomes 𝑓: 0.0013 ( 34 hom. )
Consequence
RPN1
NM_002950.4 synonymous
NM_002950.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.16
Genes affected
RPN1 (HGNC:10381): (ribophorin I) 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 forms part of the regulatory subunit of the 26S proteasome and may mediate binding of ubiquitin-like domains to this proteasome. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
Variant 3-128620588-G-A is Benign according to our data. Variant chr3-128620588-G-A is described in ClinVar as [Benign]. Clinvar id is 720033.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-2.16 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0128 (1951/152216) while in subpopulation AFR AF= 0.0432 (1796/41526). AF 95% confidence interval is 0.0416. There are 40 homozygotes in gnomad4. There are 903 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 40 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPN1 | NM_002950.4 | c.1647C>T | p.Ser549= | synonymous_variant | 10/10 | ENST00000296255.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPN1 | ENST00000296255.8 | c.1647C>T | p.Ser549= | synonymous_variant | 10/10 | 1 | NM_002950.4 | P1 | |
RPN1 | ENST00000497289.5 | c.1131C>T | p.Ser377= | synonymous_variant | 10/10 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0128 AC: 1950AN: 152098Hom.: 40 Cov.: 32
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GnomAD3 exomes AF: 0.00348 AC: 862AN: 247462Hom.: 15 AF XY: 0.00245 AC XY: 329AN XY: 134028
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GnomAD4 exome AF: 0.00126 AC: 1843AN: 1460464Hom.: 34 Cov.: 31 AF XY: 0.00107 AC XY: 775AN XY: 726448
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GnomAD4 genome ? AF: 0.0128 AC: 1951AN: 152216Hom.: 40 Cov.: 32 AF XY: 0.0121 AC XY: 903AN XY: 74408
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3478
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Apr 30, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at