rs374312736
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_000135.4(FANCA):c.2222+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000165 in 1,604,520 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_000135.4 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 |
---|---|---|---|---|---|---|---|---|
FANCA | NM_000135.4 | c.2222+7G>A | splice_region_variant, intron_variant | ENST00000389301.8 | NP_000126.2 | |||
FANCA | NM_001286167.3 | c.2222+7G>A | splice_region_variant, intron_variant | NP_001273096.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FANCA | ENST00000389301.8 | c.2222+7G>A | splice_region_variant, intron_variant | 1 | NM_000135.4 | ENSP00000373952.3 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152184Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000772 AC: 18AN: 233232Hom.: 0 AF XY: 0.0000712 AC XY: 9AN XY: 126448
GnomAD4 exome AF: 0.000175 AC: 254AN: 1452336Hom.: 0 Cov.: 32 AF XY: 0.000164 AC XY: 118AN XY: 721612
GnomAD4 genome AF: 0.0000723 AC: 11AN: 152184Hom.: 0 Cov.: 31 AF XY: 0.0000673 AC XY: 5AN XY: 74342
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 07, 2017 | - - |
Fanconi anemia complementation group A Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Fanconi anemia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
FANCA-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 29, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at