rs12634123
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001457.4(FLNB):c.6889-18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 1,612,544 control chromosomes in the GnomAD database, including 335,250 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.64 ( 31631 hom., cov: 32)
Exomes 𝑓: 0.64 ( 303619 hom. )
Consequence
FLNB
NM_001457.4 intron
NM_001457.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.113
Genes affected
FLNB (HGNC:3755): (filamin B) This gene encodes a member of the filamin family. The encoded protein interacts with glycoprotein Ib alpha as part of the process to repair vascular injuries. The platelet glycoprotein Ib complex includes glycoprotein Ib alpha, and it binds the actin cytoskeleton. Mutations in this gene have been found in several conditions: atelosteogenesis type 1 and type 3; boomerang dysplasia; autosomal dominant Larsen syndrome; and spondylocarpotarsal synostosis syndrome. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, Nov 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
Variant 3-58159536-G-A is Benign according to our data. Variant chr3-58159536-G-A is described in ClinVar as [Benign]. Clinvar id is 258119.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-58159536-G-A is described in Lovd as [Likely_benign]. Variant chr3-58159536-G-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNB | NM_001457.4 | c.6889-18G>A | intron_variant | ENST00000295956.9 | |||
FLNB | NM_001164317.2 | c.6982-18G>A | intron_variant | ||||
FLNB | NM_001164318.2 | c.6856-18G>A | intron_variant | ||||
FLNB | NM_001164319.2 | c.6817-18G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNB | ENST00000295956.9 | c.6889-18G>A | intron_variant | 1 | NM_001457.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.640 AC: 97172AN: 151944Hom.: 31602 Cov.: 32
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GnomAD3 exomes AF: 0.672 AC: 168874AN: 251232Hom.: 58543 AF XY: 0.669 AC XY: 90888AN XY: 135836
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GnomAD4 exome AF: 0.640 AC: 935294AN: 1460482Hom.: 303619 Cov.: 39 AF XY: 0.642 AC XY: 466791AN XY: 726608
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GnomAD4 genome ? AF: 0.640 AC: 97251AN: 152062Hom.: 31631 Cov.: 32 AF XY: 0.644 AC XY: 47819AN XY: 74308
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 01, 2016 | 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. - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 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