rs193922196
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_000138.5(FBN1):c.3082+8delG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00061 in 1,612,022 control chromosomes in the GnomAD database, including 4 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000138.5 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00328 AC: 499AN: 152208Hom.: 2 Cov.: 31
GnomAD3 exomes AF: 0.000851 AC: 213AN: 250156Hom.: 1 AF XY: 0.000561 AC XY: 76AN XY: 135396
GnomAD4 exome AF: 0.000330 AC: 482AN: 1459696Hom.: 2 Cov.: 31 AF XY: 0.000249 AC XY: 181AN XY: 726290
GnomAD4 genome AF: 0.00329 AC: 501AN: 152326Hom.: 2 Cov.: 31 AF XY: 0.00299 AC XY: 223AN XY: 74496
ClinVar
Submissions by phenotype
not specified Benign:4
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3082+8delG in intron 24 of FBN1: This variant has not been previously reported, but is not expected to be of clinical significance because it is not located in the conserved region of the splicing consensus sequence. -
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Familial thoracic aortic aneurysm and aortic dissection Benign:3
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The variant is found in TAAD panel(s). -
This alteration is classified as 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. -
Marfan syndrome Uncertain:1Benign:1
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not provided Benign:1
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FBN1-related disorder Benign:1
This variant is classified as 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