chr3-58008763-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP2
The NM_001457.4(FLNB):c.199C>T(p.His67Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,680 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
FLNB
NM_001457.4 missense
NM_001457.4 missense
Scores
2
13
3
Clinical Significance
Conservation
PhyloP100: 2.95
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 Uncertain_significance. Variant got 5 ACMG points.
PM1
In a region_of_interest Actin-binding (size 238) in uniprot entity FLNB_HUMAN there are 58 pathogenic changes around while only 5 benign (92%) in NM_001457.4
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, FLNB
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNB | NM_001457.4 | c.199C>T | p.His67Tyr | missense_variant | 1/46 | ENST00000295956.9 | |
FLNB | NM_001164317.2 | c.199C>T | p.His67Tyr | missense_variant | 1/47 | ||
FLNB | NM_001164318.2 | c.199C>T | p.His67Tyr | missense_variant | 1/46 | ||
FLNB | NM_001164319.2 | c.199C>T | p.His67Tyr | missense_variant | 1/45 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNB | ENST00000295956.9 | c.199C>T | p.His67Tyr | missense_variant | 1/46 | 1 | NM_001457.4 | A1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251338Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135862
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461680Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727114
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GnomAD4 genome Cov.: 33
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33
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Boomerang dysplasia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Aug 07, 2018 | - - |
Larsen syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Aug 07, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Benign
L;L;L;L
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
1.0, 1.0
.;D;D;.
Vest4
MutPred
Loss of glycosylation at P70 (P = 0.0359);Loss of glycosylation at P70 (P = 0.0359);Loss of glycosylation at P70 (P = 0.0359);Loss of glycosylation at P70 (P = 0.0359);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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