rs777132952
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_022489.4(INF2):c.1950-3C>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000292 in 1,611,406 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 Uncertain significance (★★).
Frequency
Consequence
NM_022489.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INF2 | NM_022489.4 | c.1950-3C>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000392634.9 | |||
INF2 | NM_001031714.4 | c.1950-3C>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INF2 | ENST00000392634.9 | c.1950-3C>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_022489.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152218Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000243 AC: 6AN: 247014Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134492
GnomAD4 exome AF: 0.0000267 AC: 39AN: 1459188Hom.: 0 Cov.: 32 AF XY: 0.0000289 AC XY: 21AN XY: 725904
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152218Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74362
ClinVar
Submissions by phenotype
Focal segmental glomerulosclerosis 5;C4302667:Charcot-Marie-Tooth disease dominant intermediate E Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 27, 2023 | This sequence change falls in intron 10 of the INF2 gene. It does not directly change the encoded amino acid sequence of the INF2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs777132952, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with INF2-related conditions. ClinVar contains an entry for this variant (Variation ID: 581537). 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 is not likely to affect RNA splicing. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 14, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at