4-54727819-A-G
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_000222.3(KIT):c.1775-4A>G 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 0.00000869 in 1,611,220 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_000222.3 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIT | NM_000222.3 | c.1775-4A>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000288135.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIT | ENST00000288135.6 | c.1775-4A>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000222.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152022Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251066Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135690
GnomAD4 exome AF: 0.00000891 AC: 13AN: 1459198Hom.: 0 Cov.: 32 AF XY: 0.00000689 AC XY: 5AN XY: 726014
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152022Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74240
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 03, 2019 | The c.1775-4A>G intronic variant results from an A to G substitution 4 nucleotides upstream from coding exon 12 in the KIT gene. This nucleotide position is poorly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice acceptor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Gastrointestinal stromal tumor Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 20, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at