rs8018014
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_020937.4(FANCM):āc.6141T>Cā(p.Asp2047=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0167 in 1,606,780 control chromosomes in the GnomAD database, including 396 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.028 ( 133 hom., cov: 32)
Exomes š: 0.015 ( 263 hom. )
Consequence
FANCM
NM_020937.4 synonymous
NM_020937.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.614
Genes affected
FANCM (HGNC:23168): (FA complementation group M) 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 M. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
?
Variant 14-45200002-T-C is Benign according to our data. Variant chr14-45200002-T-C is described in ClinVar as [Benign]. Clinvar id is 261392.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-45200002-T-C is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.614 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0695 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCM | NM_020937.4 | c.6141T>C | p.Asp2047= | synonymous_variant | 23/23 | ENST00000267430.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCM | ENST00000267430.10 | c.6141T>C | p.Asp2047= | synonymous_variant | 23/23 | 1 | NM_020937.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0284 AC: 4323AN: 152180Hom.: 132 Cov.: 32
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GnomAD3 exomes AF: 0.0139 AC: 3497AN: 251028Hom.: 74 AF XY: 0.0127 AC XY: 1720AN XY: 135720
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GnomAD4 exome AF: 0.0155 AC: 22513AN: 1454482Hom.: 263 Cov.: 28 AF XY: 0.0149 AC XY: 10818AN XY: 724026
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GnomAD4 genome ? AF: 0.0285 AC: 4335AN: 152298Hom.: 133 Cov.: 32 AF XY: 0.0264 AC XY: 1963AN XY: 74478
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ClinVar
Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Mar 26, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Mar 29, 2017 | - - |
Premature ovarian failure 15 Benign:1
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Fanconi anemia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 24, 2019 | - - |
Computational scores
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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
Find out detailed SpliceAI scores and Pangolin per-transcript scores at