chr1-89120286-A-C
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_004120.5(GBP2):c.321T>G(p.Gly107Gly) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000079 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
GBP2
NM_004120.5 splice_region, synonymous
NM_004120.5 splice_region, synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.16
Genes affected
GBP2 (HGNC:4183): (guanylate binding protein 2) This gene belongs to the guanine-binding protein (GBP) family, which includes interferon-induced proteins that can bind to guanine nucleotides (GMP, GDP and GTP). The encoded protein is a GTPase which hydrolyzes GTP, predominantly to GDP. The protein may play a role as a marker of squamous cell carcinomas. [provided by RefSeq, Jul 2013]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP7
Synonymous conserved (PhyloP=-4.16 with no splicing effect.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| GBP2 | ENST00000370466.4 | c.321T>G | p.Gly107Gly | splice_region_variant, synonymous_variant | Exon 4 of 11 | 1 | NM_004120.5 | ENSP00000359497.3 | ||
| GBP2 | ENST00000464839.5 | n.321T>G | splice_region_variant, non_coding_transcript_exon_variant | Exon 7 of 15 | 2 | ENSP00000434282.1 | ||||
| GBP2 | ENST00000463660.1 | n.-66T>G | upstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.000263 AC: 66AN: 251132 AF XY: 0.000162 show subpopulations
GnomAD2 exomes
AF:
AC:
66
AN:
251132
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000788 AC: 115AN: 1459084Hom.: 0 Cov.: 28 AF XY: 0.0000661 AC XY: 48AN XY: 726084 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
115
AN:
1459084
Hom.:
Cov.:
28
AF XY:
AC XY:
48
AN XY:
726084
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33396
American (AMR)
AF:
AC:
0
AN:
44704
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26104
East Asian (EAS)
AF:
AC:
0
AN:
39676
South Asian (SAS)
AF:
AC:
1
AN:
86202
European-Finnish (FIN)
AF:
AC:
113
AN:
53318
Middle Eastern (MID)
AF:
AC:
0
AN:
5758
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1109632
Other (OTH)
AF:
AC:
1
AN:
60294
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.302
Heterozygous variant carriers
0
12
23
35
46
58
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
not provided Uncertain:1
-
Richard Lifton Laboratory, Yale University School of Medicine
Significance:Uncertain significance
Review Status:no assertion criteria provided
Collection Method:literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
Loading publications...