chr22-36937930-GC-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 4P and 5B. PVS1_StrongBP6BS2
The NM_000395.3(CSF2RB):c.2124delC(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
Consequence
NM_000395.3 frameshift
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CSF2RB | ENST00000403662.8 | c.2124delC | p.Ser709LeufsTer22 | frameshift_variant | Exon 14 of 14 | 5 | NM_000395.3 | ENSP00000384053.3 | ||
CSF2RB | ENST00000406230.5 | c.2142delC | p.Ser715LeufsTer22 | frameshift_variant | Exon 13 of 13 | 1 | ENSP00000385271.1 |
Frequencies
GnomAD3 genomes AF: 0.00118 AC: 179AN: 152148Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00183 AC: 461AN: 251406Hom.: 2 AF XY: 0.00178 AC XY: 242AN XY: 135888
GnomAD4 exome AF: 0.00113 AC: 1653AN: 1461870Hom.: 9 Cov.: 35 AF XY: 0.00114 AC XY: 830AN XY: 727232
GnomAD4 genome AF: 0.00118 AC: 179AN: 152268Hom.: 1 Cov.: 32 AF XY: 0.00105 AC XY: 78AN XY: 74462
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
- -
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) -
not specified Uncertain:1
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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at