rs542953863
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_000138.5(FBN1):c.6054C>T(p.Val2018Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000855 in 1,613,288 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000138.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000592 AC: 9AN: 152146Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000132 AC: 33AN: 250532Hom.: 0 AF XY: 0.000199 AC XY: 27AN XY: 135400
GnomAD4 exome AF: 0.0000883 AC: 129AN: 1461142Hom.: 1 Cov.: 32 AF XY: 0.000127 AC XY: 92AN XY: 726898
GnomAD4 genome AF: 0.0000592 AC: 9AN: 152146Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8AN XY: 74318
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Benign:3
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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. -
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Connective tissue disorder Uncertain:1
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Marfan syndrome Benign:1
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not specified Benign:1
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. -
not provided Benign:1
FBN1: BP4, BP7, BS1 -
FBN1-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Marfan syndrome;C4707243:Familial thoracic aortic aneurysm and aortic dissection Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at