22-45541269-C-T
Variant names:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_006486.3(FBLN1):c.963C>T(p.Ile321Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 1,613,910 control chromosomes in the GnomAD database, including 126,079 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.36 ( 10329 hom., cov: 34)
Exomes 𝑓: 0.39 ( 115750 hom. )
Consequence
FBLN1
NM_006486.3 synonymous
NM_006486.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.24
Genes affected
FBLN1 (HGNC:3600): (fibulin 1) Fibulin 1 is a secreted glycoprotein that becomes incorporated into a fibrillar extracellular matrix. Calcium-binding is apparently required to mediate its binding to laminin and nidogen. It mediates platelet adhesion via binding fibrinogen. Four splice variants which differ in the 3' end have been identified. Each variant encodes a different isoform, but no functional distinctions have been identified among the four variants. [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=-0.78).
BP6
Variant 22-45541269-C-T is Benign according to our data. Variant chr22-45541269-C-T is described in ClinVar as [Benign]. Clinvar id is 1232901.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-45541269-C-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-2.24 with no splicing effect.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FBLN1 | NM_006486.3 | c.963C>T | p.Ile321Ile | synonymous_variant | Exon 9 of 17 | ENST00000327858.11 | NP_006477.3 | |
FBLN1 | NM_001996.4 | c.963C>T | p.Ile321Ile | synonymous_variant | Exon 9 of 15 | NP_001987.3 | ||
FBLN1 | NM_006485.4 | c.963C>T | p.Ile321Ile | synonymous_variant | Exon 9 of 15 | NP_006476.3 | ||
FBLN1 | NM_006487.3 | c.963C>T | p.Ile321Ile | synonymous_variant | Exon 9 of 15 | NP_006478.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.356 AC: 54085AN: 152040Hom.: 10333 Cov.: 34
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GnomAD3 exomes AF: 0.358 AC: 90055AN: 251468Hom.: 17578 AF XY: 0.366 AC XY: 49676AN XY: 135912
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GnomAD4 exome AF: 0.392 AC: 573066AN: 1461750Hom.: 115750 Cov.: 49 AF XY: 0.392 AC XY: 285268AN XY: 727190
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GnomAD4 genome AF: 0.355 AC: 54076AN: 152160Hom.: 10329 Cov.: 34 AF XY: 0.357 AC XY: 26555AN XY: 74390
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided
- -
Nov 11, 2018
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Synpolydactyly type 2 Benign:1
Aug 10, 2021
Genome-Nilou Lab
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at