rs397515761
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_000138.5(FBN1):c.165-7G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000561 in 1,603,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000138.5 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBN1 | NM_000138.5 | c.165-7G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000316623.10 | |||
FBN1 | NM_001406716.1 | c.165-7G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
FBN1 | NM_001406717.1 | c.165-7G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN1 | ENST00000316623.10 | c.165-7G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000138.5 | P1 | |||
FBN1 | ENST00000559133.6 | c.165-7G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant | 1 | |||||
FBN1 | ENST00000537463.6 | c.165-7G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant | 5 | |||||
FBN1 | ENST00000674301.2 | c.165-7G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151660Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 249032Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135098
GnomAD4 exome AF: 0.0000606 AC: 88AN: 1451704Hom.: 0 Cov.: 28 AF XY: 0.0000526 AC XY: 38AN XY: 723008
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151660Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74006
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 30, 2012 | Variant classified as Uncertain Significance - Favor Benign. The 165-7G>A varian t has not been reported in the literature nor previously identified by our labor atory. This variant is located in the 3' splice region and computational tools do not predict altered splicing. However, this information is not predictive eno ugh to rule out pathogenicity. Therefore, the clinical significance of this var iant cannot be determined at this time, although we would lean towards a more be nign role. - |
Marfan syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Aug 15, 2023 | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Nov 16, 2018 | - - |
Marfan syndrome;C4707243:Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at