5-132484497-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_002198.3(IRF1):c.718C>A(p.Leu240Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict 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_002198.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IRF1 | NM_002198.3 | c.718C>A | p.Leu240Ile | missense_variant, splice_region_variant | 9/10 | ENST00000245414.9 | NP_002189.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IRF1 | ENST00000245414.9 | c.718C>A | p.Leu240Ile | missense_variant, splice_region_variant | 9/10 | 1 | NM_002198.3 | ENSP00000245414 | P1 | |
IRF1-AS1 | ENST00000612967.2 | n.281-1695G>T | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251384Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135858
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461824Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727210
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 06, 2024 | The c.718C>A (p.L240I) alteration is located in exon 9 (coding exon 8) of the IRF1 gene. This alteration results from a C to A substitution at nucleotide position 718, causing the leucine (L) at amino acid position 240 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at