rs141278771
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7
The NM_000135.4(FANCA):c.3981C>T(p.His1327=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000526 in 1,551,404 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00041 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00054 ( 3 hom. )
Consequence
FANCA
NM_000135.4 synonymous
NM_000135.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.327
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]
ZNF276 (HGNC:23330): (zinc finger protein 276) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in kinetochore. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 16-89739507-G-A is Benign according to our data. Variant chr16-89739507-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 215634.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=6, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=-0.327 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCA | NM_000135.4 | c.3981C>T | p.His1327= | synonymous_variant | 40/43 | ENST00000389301.8 | |
ZNF276 | NM_001113525.2 | c.*1261G>A | 3_prime_UTR_variant | 11/11 | ENST00000443381.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCA | ENST00000389301.8 | c.3981C>T | p.His1327= | synonymous_variant | 40/43 | 1 | NM_000135.4 | P1 | |
ZNF276 | ENST00000443381.7 | c.*1261G>A | 3_prime_UTR_variant | 11/11 | 1 | NM_001113525.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000407 AC: 62AN: 152232Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000391 AC: 61AN: 155984Hom.: 0 AF XY: 0.000389 AC XY: 32AN XY: 82250
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GnomAD4 exome AF: 0.000539 AC: 754AN: 1399054Hom.: 3 Cov.: 33 AF XY: 0.000529 AC XY: 365AN XY: 690096
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:6
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Fanconi anemia complementation group A Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Jan 28, 2022 | This variant has not been reported in the literature but is present in 0.06% (42/75386) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/16-89805915-G-A?dataset=gnomad_r2_1) and in ClinVar (Variation ID:215634). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. Of note, this variant is a silent variant and does not change the amino acid, reducing the probability that this variant is disease causing. In summary, data on this variant suggests that this variant does not cause disease but requires further evidence. Therefore, this variant is classified as Likely Benign. - |
Fanconi anemia Benign:2
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | May 19, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Apr 18, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | FANCA: BP4, BP7 - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | May 27, 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
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at