4-1805673-G-C
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_000142.5(FGFR3):c.1645+4G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,612,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000142.5 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FGFR3 | NM_000142.5 | c.1645+4G>C | splice_region_variant, intron_variant | ENST00000440486.8 | NP_000133.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FGFR3 | ENST00000440486.8 | c.1645+4G>C | splice_region_variant, intron_variant | 5 | NM_000142.5 | ENSP00000414914.2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152254Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000280 AC: 7AN: 249604Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135262
GnomAD4 exome AF: 0.00000685 AC: 10AN: 1459818Hom.: 0 Cov.: 34 AF XY: 0.00000551 AC XY: 4AN XY: 726098
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152254Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74384
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 24, 2023 | Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 435190). This variant has not been reported in the literature in individuals affected with FGFR3-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.02%). This sequence change falls in intron 12 of the FGFR3 gene. It does not directly change the encoded amino acid sequence of the FGFR3 protein. It affects a nucleotide within the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 26, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at