rs7142192
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_020937.4(FANCM):c.5190G>A(p.Gln1730=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,614,114 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0086 ( 17 hom., cov: 32)
Exomes 𝑓: 0.00097 ( 19 hom. )
Consequence
FANCM
NM_020937.4 synonymous
NM_020937.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.477
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=-0.84).
BP6
?
Variant 14-45189212-G-A is Benign according to our data. Variant chr14-45189212-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 210990.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-45189212-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.477 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00858 (1307/152262) while in subpopulation AFR AF= 0.0299 (1241/41542). AF 95% confidence interval is 0.0285. There are 17 homozygotes in gnomad4. There are 593 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 17 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCM | NM_020937.4 | c.5190G>A | p.Gln1730= | synonymous_variant | 20/23 | ENST00000267430.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCM | ENST00000267430.10 | c.5190G>A | p.Gln1730= | synonymous_variant | 20/23 | 1 | NM_020937.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00856 AC: 1302AN: 152144Hom.: 17 Cov.: 32
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GnomAD3 exomes AF: 0.00227 AC: 571AN: 251156Hom.: 6 AF XY: 0.00147 AC XY: 200AN XY: 135718
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GnomAD4 exome AF: 0.000967 AC: 1413AN: 1461852Hom.: 19 Cov.: 32 AF XY: 0.000831 AC XY: 604AN XY: 727232
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GnomAD4 genome ? AF: 0.00858 AC: 1307AN: 152262Hom.: 17 Cov.: 32 AF XY: 0.00796 AC XY: 593AN XY: 74462
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jul 07, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 01, 2020 | - - |
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
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 09, 2021 | - - |
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