chr3-58071957-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001457.4(FLNB):​c.293-5089G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 152,028 control chromosomes in the GnomAD database, including 23,026 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.53 ( 23026 hom., cov: 32)

Consequence

FLNB
NM_001457.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0730

Publications

7 publications found
Variant links:
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]
FLNB Gene-Disease associations (from GenCC):
  • atelosteogenesis type I
    Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
  • atelosteogenesis type III
    Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
  • Larsen syndrome
    Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
  • spondylocarpotarsal synostosis syndrome
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
  • Boomerang dysplasia
    Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FLNBNM_001457.4 linkc.293-5089G>T intron_variant Intron 1 of 45 ENST00000295956.9 NP_001448.2 O75369-1
FLNBNM_001164317.2 linkc.293-5089G>T intron_variant Intron 1 of 46 NP_001157789.1 O75369-8
FLNBNM_001164318.2 linkc.293-5089G>T intron_variant Intron 1 of 45 NP_001157790.1 O75369-9
FLNBNM_001164319.2 linkc.293-5089G>T intron_variant Intron 1 of 44 NP_001157791.1 O75369-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FLNBENST00000295956.9 linkc.293-5089G>T intron_variant Intron 1 of 45 1 NM_001457.4 ENSP00000295956.5 O75369-1

Frequencies

GnomAD3 genomes
AF:
0.534
AC:
81161
AN:
151908
Hom.:
22981
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.735
Gnomad AMI
AF:
0.447
Gnomad AMR
AF:
0.479
Gnomad ASJ
AF:
0.583
Gnomad EAS
AF:
0.376
Gnomad SAS
AF:
0.428
Gnomad FIN
AF:
0.419
Gnomad MID
AF:
0.618
Gnomad NFE
AF:
0.460
Gnomad OTH
AF:
0.525
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.534
AC:
81257
AN:
152028
Hom.:
23026
Cov.:
32
AF XY:
0.530
AC XY:
39408
AN XY:
74330
show subpopulations
African (AFR)
AF:
0.735
AC:
30498
AN:
41476
American (AMR)
AF:
0.479
AC:
7316
AN:
15262
Ashkenazi Jewish (ASJ)
AF:
0.583
AC:
2024
AN:
3470
East Asian (EAS)
AF:
0.376
AC:
1940
AN:
5166
South Asian (SAS)
AF:
0.428
AC:
2061
AN:
4816
European-Finnish (FIN)
AF:
0.419
AC:
4428
AN:
10560
Middle Eastern (MID)
AF:
0.633
AC:
186
AN:
294
European-Non Finnish (NFE)
AF:
0.460
AC:
31283
AN:
67964
Other (OTH)
AF:
0.528
AC:
1113
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1833
3666
5499
7332
9165
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
682
1364
2046
2728
3410
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.487
Hom.:
60345
Bravo
AF:
0.547
Asia WGS
AF:
0.407
AC:
1417
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
1.6
DANN
Benign
0.73
PhyloP100
0.073
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs9822918; hg19: chr3-58057684; API