rs2905223
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_001018113.3(FANCB):c.1327-10T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.53 ( 11742 hom., 16080 hem., cov: 21)
Exomes 𝑓: 0.58 ( 120219 hom. 169168 hem. )
Failed GnomAD Quality Control
Consequence
FANCB
NM_001018113.3 splice_polypyrimidine_tract, intron
NM_001018113.3 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00002456
2
Clinical Significance
Conservation
PhyloP100: -1.27
Genes affected
FANCB (HGNC:3583): (FA complementation group B) This gene encodes a member of the Fanconi anemia complementation group B. This protein is assembled into a nucleoprotein complex that is involved in the repair of DNA lesions. Mutations in this gene can cause chromosome instability and VACTERL syndrome with hydrocephalus. [provided by RefSeq, Apr 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
Variant X-14850684-A-G is Benign according to our data. Variant chrX-14850684-A-G is described in ClinVar as [Benign]. Clinvar id is 93467.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-14850684-A-G is described in Lovd as [Benign]. Variant chrX-14850684-A-G is described in Lovd as [Likely_benign].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCB | NM_001018113.3 | c.1327-10T>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000650831.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCB | ENST00000650831.1 | c.1327-10T>C | splice_polypyrimidine_tract_variant, intron_variant | NM_001018113.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.535 AC: 58196AN: 108757Hom.: 11746 Cov.: 21 AF XY: 0.514 AC XY: 16063AN XY: 31235
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GnomAD3 exomes AF: 0.517 AC: 78766AN: 152467Hom.: 15122 AF XY: 0.516 AC XY: 23447AN XY: 45399
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GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.576 AC: 573309AN: 995768Hom.: 120219 Cov.: 18 AF XY: 0.574 AC XY: 169168AN XY: 294908
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GnomAD4 genome ? Data not reliable, filtered out with message: InbreedingCoeff AF: 0.535 AC: 58192AN: 108802Hom.: 11742 Cov.: 21 AF XY: 0.514 AC XY: 16080AN XY: 31290
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ClinVar
Significance: Benign
Submissions summary: Benign:12
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 01, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 28, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
Fanconi anemia complementation group B Benign:3
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Fanconi anemia Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Dec 09, 2019 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 04, 2018 | - - |
VACTERL association, X-linked, with or without hydrocephalus Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
X-linked central congenital hypothyroidism with late-onset testicular enlargement Benign:1
Likely benign, no assertion criteria provided | curation | Leiden Open Variation Database | Feb 28, 2020 | Curator: Arleen D. Auerbach. Submitter to LOVD: Yu Sun. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
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