3-58120049-C-T

Variant summary

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

The NM_001457.4(FLNB):​c.2863+1060C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,154 control chromosomes in the GnomAD database, including 4,087 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 0.20 ( 4087 hom., cov: 32)

Consequence

FLNB
NM_001457.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00900

Publications

8 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=-0.87).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FLNBNM_001457.4 linkc.2863+1060C>T intron_variant Intron 19 of 45 ENST00000295956.9 NP_001448.2 O75369-1
FLNBNM_001164317.2 linkc.2863+1060C>T intron_variant Intron 19 of 46 NP_001157789.1 O75369-8
FLNBNM_001164318.2 linkc.2863+1060C>T intron_variant Intron 19 of 45 NP_001157790.1 O75369-9
FLNBNM_001164319.2 linkc.2863+1060C>T intron_variant Intron 19 of 44 NP_001157791.1 O75369-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FLNBENST00000295956.9 linkc.2863+1060C>T intron_variant Intron 19 of 45 1 NM_001457.4 ENSP00000295956.5 O75369-1

Frequencies

GnomAD3 genomes
AF:
0.205
AC:
31133
AN:
152036
Hom.:
4079
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0692
Gnomad AMI
AF:
0.170
Gnomad AMR
AF:
0.173
Gnomad ASJ
AF:
0.353
Gnomad EAS
AF:
0.0237
Gnomad SAS
AF:
0.179
Gnomad FIN
AF:
0.248
Gnomad MID
AF:
0.316
Gnomad NFE
AF:
0.295
Gnomad OTH
AF:
0.228
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.205
AC:
31148
AN:
152154
Hom.:
4087
Cov.:
32
AF XY:
0.201
AC XY:
14977
AN XY:
74384
show subpopulations
African (AFR)
AF:
0.0691
AC:
2872
AN:
41538
American (AMR)
AF:
0.173
AC:
2646
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
0.353
AC:
1224
AN:
3468
East Asian (EAS)
AF:
0.0236
AC:
122
AN:
5180
South Asian (SAS)
AF:
0.180
AC:
866
AN:
4812
European-Finnish (FIN)
AF:
0.248
AC:
2624
AN:
10580
Middle Eastern (MID)
AF:
0.327
AC:
96
AN:
294
European-Non Finnish (NFE)
AF:
0.295
AC:
20054
AN:
67968
Other (OTH)
AF:
0.231
AC:
489
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1192
2384
3577
4769
5961
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
334
668
1002
1336
1670
<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:
0.244
Hom.:
8257
Bravo
AF:
0.193
Asia WGS
AF:
0.0900
AC:
316
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
3.8
DANN
Benign
0.45
PhyloP100
0.0090
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: rs13077017; hg19: chr3-58105776; API