14-45176983-T-G
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_020937.4(FANCM):c.4222+7T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000558 in 1,507,644 control chromosomes in the GnomAD database, including 5 homozygotes. 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 Likely benign (★★).
Frequency
Consequence
NM_020937.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCM | NM_020937.4 | c.4222+7T>G | splice_region_variant, intron_variant | ENST00000267430.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCM | ENST00000267430.10 | c.4222+7T>G | splice_region_variant, intron_variant | 1 | NM_020937.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00304 AC: 462AN: 152210Hom.: 3 Cov.: 32
GnomAD3 exomes AF: 0.000687 AC: 167AN: 243188Hom.: 0 AF XY: 0.000601 AC XY: 80AN XY: 133168
GnomAD4 exome AF: 0.000278 AC: 377AN: 1355316Hom.: 1 Cov.: 21 AF XY: 0.000213 AC XY: 145AN XY: 680300
GnomAD4 genome AF: 0.00305 AC: 464AN: 152328Hom.: 4 Cov.: 32 AF XY: 0.00303 AC XY: 226AN XY: 74502
ClinVar
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Aug 12, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 11, 2021 | - - |
Fanconi anemia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
FANCM-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 18, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | May 30, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at