rs75940000
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The ENST00000262464.9(FBN2):c.1749G>A(p.Gly583=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000106 in 1,613,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00058 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000057 ( 0 hom. )
Consequence
FBN2
ENST00000262464.9 synonymous
ENST00000262464.9 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.20
Genes affected
FBN2 (HGNC:3604): (fibrillin 2) The protein encoded by this gene is a component of connective tissue microfibrils and may be involved in elastic fiber assembly. Mutations in this gene cause congenital contractural arachnodactyly. [provided by RefSeq, Jul 2008]
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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=-0.73).
BP6
Variant 5-128377852-C-T is Benign according to our data. Variant chr5-128377852-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 213222.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-4.2 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000578 (88/152186) while in subpopulation AFR AF= 0.00207 (86/41524). AF 95% confidence interval is 0.00172. There are 0 homozygotes in gnomad4. There are 33 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 88 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FBN2 | NM_001999.4 | c.1749G>A | p.Gly583= | synonymous_variant | 13/65 | ENST00000262464.9 | NP_001990.2 | |
FBN2 | XM_017009228.3 | c.1596G>A | p.Gly532= | synonymous_variant | 12/64 | XP_016864717.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FBN2 | ENST00000262464.9 | c.1749G>A | p.Gly583= | synonymous_variant | 13/65 | 1 | NM_001999.4 | ENSP00000262464 | P1 | |
FBN2 | ENST00000508989.5 | c.1650G>A | p.Gly550= | synonymous_variant | 12/33 | 2 | ENSP00000425596 | |||
FBN2 | ENST00000511489.1 | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.000579 AC: 88AN: 152068Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000135 AC: 34AN: 251060Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135674
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GnomAD4 exome AF: 0.0000568 AC: 83AN: 1461224Hom.: 0 Cov.: 31 AF XY: 0.0000440 AC XY: 32AN XY: 726926
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GnomAD4 genome AF: 0.000578 AC: 88AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.000444 AC XY: 33AN XY: 74404
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 14, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 30, 2017 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Congenital contractural arachnodactyly Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
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