rs34324145
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_003999.3(OSMR):c.1307T>A(p.Val436Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00339 in 1,613,678 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0023 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0035 ( 14 hom. )
Consequence
OSMR
NM_003999.3 missense
NM_003999.3 missense
Scores
4
7
8
Clinical Significance
Conservation
PhyloP100: 1.82
Genes affected
OSMR (HGNC:8507): (oncostatin M receptor) This gene encodes a member of the type I cytokine receptor family. The encoded protein heterodimerizes with interleukin 6 signal transducer to form the type II oncostatin M receptor and with interleukin 31 receptor A to form the interleukin 31 receptor, and thus transduces oncostatin M and interleukin 31 induced signaling events. Mutations in this gene have been associated with familial primary localized cutaneous amyloidosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.013510972).
BP6
Variant 5-38917567-T-A is Benign according to our data. Variant chr5-38917567-T-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 719321.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1, Benign=1}.
BS2
High Homozygotes in GnomAdExome4 at 14 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OSMR | NM_003999.3 | c.1307T>A | p.Val436Asp | missense_variant | 10/18 | ENST00000274276.8 | NP_003990.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OSMR | ENST00000274276.8 | c.1307T>A | p.Val436Asp | missense_variant | 10/18 | 1 | NM_003999.3 | ENSP00000274276.3 | ||
OSMR | ENST00000513831.1 | c.128T>A | p.Val43Asp | missense_variant | 2/4 | 3 | ENSP00000423913.1 |
Frequencies
GnomAD3 genomes AF: 0.00227 AC: 346AN: 152224Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00232 AC: 584AN: 251456Hom.: 2 AF XY: 0.00222 AC XY: 302AN XY: 135894
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GnomAD4 exome AF: 0.00351 AC: 5125AN: 1461336Hom.: 14 Cov.: 31 AF XY: 0.00326 AC XY: 2372AN XY: 726986
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GnomAD4 genome AF: 0.00227 AC: 346AN: 152342Hom.: 0 Cov.: 32 AF XY: 0.00197 AC XY: 147AN XY: 74494
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 12, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 31, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | OSMR: BP4, BS1, BS2 - |
OSMR-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 04, 2020 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
T;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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