rs1800333
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000135.4(FANCA):c.1626+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000518 in 1,611,346 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0028 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00028 ( 3 hom. )
Consequence
FANCA
NM_000135.4 intron
NM_000135.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.223
Genes affected
FANCA (HGNC:3582): (FA complementation group A) The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group A. Alternative splicing results in multiple transcript variants encoding different isoforms. Mutations in this gene are the most common cause of Fanconi anemia. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
Variant 16-89782843-G-A is Benign according to our data. Variant chr16-89782843-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 255236.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0028 (426/152318) while in subpopulation AFR AF= 0.00996 (414/41564). AF 95% confidence interval is 0.00917. There are 2 homozygotes in gnomad4. There are 202 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCA | NM_000135.4 | c.1626+16C>T | intron_variant | ENST00000389301.8 | |||
FANCA | NM_001286167.3 | c.1626+16C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCA | ENST00000389301.8 | c.1626+16C>T | intron_variant | 1 | NM_000135.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00277 AC: 421AN: 152200Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000709 AC: 178AN: 251198Hom.: 0 AF XY: 0.000434 AC XY: 59AN XY: 135812
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GnomAD4 exome AF: 0.000280 AC: 408AN: 1459028Hom.: 3 Cov.: 31 AF XY: 0.000233 AC XY: 169AN XY: 726008
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Fanconi anemia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Fanconi anemia complementation group A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 24, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at