rs753766357
Variant names:
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong
The NM_000135.4(FANCA):c.2317-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000608 in 1,612,602 control chromosomes in the GnomAD database, including 1 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
Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000062 ( 1 hom. )
Consequence
FANCA
NM_000135.4 splice_region, intron
NM_000135.4 splice_region, intron
Scores
2
Splicing: ADA: 0.00005583
2
Clinical Significance
Conservation
PhyloP100: -0.145
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=-0.93).
BP6
Variant 16-89770032-G-A is Benign according to our data. Variant chr16-89770032-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 456095.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| FANCA | NM_000135.4 | c.2317-8C>T | splice_region_variant, intron_variant | Intron 25 of 42 | ENST00000389301.8 | NP_000126.2 | ||
| FANCA | NM_001286167.3 | c.2317-8C>T | splice_region_variant, intron_variant | Intron 25 of 42 | NP_001273096.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.0000526 AC: 8AN: 152208Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000489 AC: 12AN: 245646Hom.: 0 AF XY: 0.0000674 AC XY: 9AN XY: 133452
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GnomAD4 exome AF: 0.0000616 AC: 90AN: 1460276Hom.: 1 Cov.: 35 AF XY: 0.0000661 AC XY: 48AN XY: 726414
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GnomAD4 genome 0.0000525 AC: 8AN: 152326Hom.: 0 Cov.: 33 AF XY: 0.0000805 AC XY: 6AN XY: 74494
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ClinVar
Significance: Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Aug 02, 2019
Genetic Services Laboratory, University of Chicago
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Fanconi anemia Benign:1
Dec 02, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Fanconi anemia complementation group A Benign:1
May 03, 2022
Fulgent Genetics, Fulgent Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
FANCA-related disorder Benign:1
Nov 18, 2019
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
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). -
not provided Benign:1
Mar 22, 2023
Quest Diagnostics Nichols Institute San Juan Capistrano
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
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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