chr4-2832353-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001122681.2(SH3BP2):c.1429C>T(p.Arg477Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00452 in 1,613,938 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R477Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_001122681.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SH3BP2 | NM_001122681.2 | c.1429C>T | p.Arg477Trp | missense_variant | 11/13 | ENST00000503393.8 | |
SH3BP2 | NM_001145856.2 | c.1600C>T | p.Arg534Trp | missense_variant | 11/13 | ||
SH3BP2 | NM_001145855.2 | c.1513C>T | p.Arg505Trp | missense_variant | 11/13 | ||
SH3BP2 | NM_003023.4 | c.1429C>T | p.Arg477Trp | missense_variant | 11/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SH3BP2 | ENST00000503393.8 | c.1429C>T | p.Arg477Trp | missense_variant | 11/13 | 1 | NM_001122681.2 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00306 AC: 466AN: 152180Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.00455 AC: 1143AN: 251430Hom.: 7 AF XY: 0.00525 AC XY: 713AN XY: 135906
GnomAD4 exome AF: 0.00467 AC: 6824AN: 1461640Hom.: 32 Cov.: 32 AF XY: 0.00505 AC XY: 3675AN XY: 727134
GnomAD4 genome AF: 0.00304 AC: 463AN: 152298Hom.: 2 Cov.: 32 AF XY: 0.00270 AC XY: 201AN XY: 74464
ClinVar
Submissions by phenotype
Fibrous dysplasia of jaw Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not specified Benign:1
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
not provided Benign:1
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at