rs568607741
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2
The NM_000395.3(CSF2RB):c.2124del(p.Ser709LeufsTer22) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,614,138 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0012 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 9 hom. )
Consequence
CSF2RB
NM_000395.3 frameshift
NM_000395.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.281
Genes affected
CSF2RB (HGNC:2436): (colony stimulating factor 2 receptor subunit beta) The protein encoded by this gene is the common beta chain of the high affinity receptor for IL-3, IL-5 and CSF. Defects in this gene have been reported to be associated with protein alveolar proteinosis (PAP). [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP6
Variant 22-36937930-GC-G is Benign according to our data. Variant chr22-36937930-GC-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 402566.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=2}.
BS2
High Homozygotes in GnomAdExome4 at 9 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CSF2RB | NM_000395.3 | c.2124del | p.Ser709LeufsTer22 | frameshift_variant | 14/14 | ENST00000403662.8 | NP_000386.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CSF2RB | ENST00000403662.8 | c.2124del | p.Ser709LeufsTer22 | frameshift_variant | 14/14 | 5 | NM_000395.3 | ENSP00000384053 | P1 | |
CSF2RB | ENST00000406230.5 | c.2142del | p.Ser715LeufsTer22 | frameshift_variant | 13/13 | 1 | ENSP00000385271 |
Frequencies
GnomAD3 genomes AF: 0.00118 AC: 179AN: 152148Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00183 AC: 461AN: 251406Hom.: 2 AF XY: 0.00178 AC XY: 242AN XY: 135888
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GnomAD4 exome AF: 0.00113 AC: 1653AN: 1461870Hom.: 9 Cov.: 35 AF XY: 0.00114 AC XY: 830AN XY: 727232
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GnomAD4 genome AF: 0.00118 AC: 179AN: 152268Hom.: 1 Cov.: 32 AF XY: 0.00105 AC XY: 78AN XY: 74462
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 03, 2023 | Variant proposed as a risk allele for Crohn's disease in the Ashkenazi Jewish population (Chuang et al., 2016; Levine et al., 2016); Published functional studies suggest a damaging effect, as intestinal monocytes from carriers of this variant had reduced responses to granulocyte-macrophage colony-stimulating factor (Chuang et al., 2016); Frameshift variant predicted to result in protein truncation as the last 189 amino acids are lost and replaced with 21 incorrect amino acids, although loss-of-function variants have not been reported downstream of this position in the protein; This variant is associated with the following publications: (PMID: 27377463, 34426522, 27373512, 34662886) - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 05, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Gene associated with Pulmonary alveolar proteinosis, but frequency is too high for disorder, and this is a frameshift in the last exon. Limited evidence for gene-disease association. One LOF variant has been reported, but frequency of this variant is too high for pathogenic role in this disease. - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at