rs17227361
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP6_Very_StrongBS1
The NM_000135.4(FANCA):c.3891G>A(p.Lys1297Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000505 in 1,614,212 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 0.0026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00028 ( 1 hom. )
Consequence
FANCA
NM_000135.4 synonymous
NM_000135.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.61
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 Benign. Variant got -10 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 16-89740037-C-T is Benign according to our data. Variant chr16-89740037-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 414831.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 = 0.00263 (401/152332) while in subpopulation AFR AF= 0.00912 (379/41576). AF 95% confidence interval is 0.00836. There are 0 homozygotes in gnomad4. There are 189 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FANCA | NM_000135.4 | c.3891G>A | p.Lys1297Lys | synonymous_variant | 39/43 | ENST00000389301.8 | NP_000126.2 | |
ZNF276 | NM_001113525.2 | c.*1791C>T | 3_prime_UTR_variant | 11/11 | ENST00000443381.7 | NP_001106997.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FANCA | ENST00000389301.8 | c.3891G>A | p.Lys1297Lys | synonymous_variant | 39/43 | 1 | NM_000135.4 | ENSP00000373952.3 | ||
ZNF276 | ENST00000443381.7 | c.*1791C>T | 3_prime_UTR_variant | 11/11 | 1 | NM_001113525.2 | ENSP00000415836.2 |
Frequencies
GnomAD3 genomes AF: 0.00264 AC: 402AN: 152214Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000712 AC: 179AN: 251492Hom.: 0 AF XY: 0.000456 AC XY: 62AN XY: 135918
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GnomAD4 exome AF: 0.000283 AC: 414AN: 1461880Hom.: 1 Cov.: 33 AF XY: 0.000246 AC XY: 179AN XY: 727240
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GnomAD4 genome AF: 0.00263 AC: 401AN: 152332Hom.: 0 Cov.: 32 AF XY: 0.00254 AC XY: 189AN XY: 74498
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Fanconi anemia Benign:3
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 09, 2019 | - - |
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Dec 15, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jun 04, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | May 26, 2021 | - - |
Fanconi anemia complementation group A Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 23, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: -43
Find out detailed SpliceAI scores and Pangolin per-transcript scores at