16-89808288-C-T
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong
The NM_000135.4(FANCA):c.596+6G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000589 in 1,613,434 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000060 ( 1 hom. )
Consequence
FANCA
NM_000135.4 splice_donor_region, intron
NM_000135.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.00003040
2
Clinical Significance
Conservation
PhyloP100: -1.20
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 -10 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant 16-89808288-C-T is Benign according to our data. Variant chr16-89808288-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 456133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCA | NM_000135.4 | c.596+6G>A | splice_donor_region_variant, intron_variant | ENST00000389301.8 | |||
FANCA | NM_001018112.3 | c.596+6G>A | splice_donor_region_variant, intron_variant | ||||
FANCA | NM_001286167.3 | c.596+6G>A | splice_donor_region_variant, intron_variant | ||||
FANCA | NM_001351830.2 | c.500+6G>A | splice_donor_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCA | ENST00000389301.8 | c.596+6G>A | splice_donor_region_variant, intron_variant | 1 | NM_000135.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152140Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000266 AC: 67AN: 251472Hom.: 1 AF XY: 0.000184 AC XY: 25AN XY: 135914
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GnomAD4 exome AF: 0.0000602 AC: 88AN: 1461176Hom.: 1 Cov.: 32 AF XY: 0.0000495 AC XY: 36AN XY: 726928
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Fanconi anemia Benign:2
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Jun 04, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Nov 29, 2022 | - - |
Computational scores
Source:
Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at