rs9834312

Variant summary

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

The NM_001457.4(FLNB):​c.984+764G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 152,020 control chromosomes in the GnomAD database, including 15,323 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 0.43 ( 15323 hom., cov: 32)

Consequence

FLNB
NM_001457.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.15

Publications

10 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=-0.89).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FLNBNM_001457.4 linkc.984+764G>A intron_variant Intron 6 of 45 ENST00000295956.9 NP_001448.2 O75369-1
FLNBNM_001164317.2 linkc.984+764G>A intron_variant Intron 6 of 46 NP_001157789.1 O75369-8
FLNBNM_001164318.2 linkc.984+764G>A intron_variant Intron 6 of 45 NP_001157790.1 O75369-9
FLNBNM_001164319.2 linkc.984+764G>A intron_variant Intron 6 of 44 NP_001157791.1 O75369-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FLNBENST00000295956.9 linkc.984+764G>A intron_variant Intron 6 of 45 1 NM_001457.4 ENSP00000295956.5 O75369-1

Frequencies

GnomAD3 genomes
AF:
0.426
AC:
64658
AN:
151902
Hom.:
15299
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.489
Gnomad AMI
AF:
0.490
Gnomad AMR
AF:
0.537
Gnomad ASJ
AF:
0.283
Gnomad EAS
AF:
0.922
Gnomad SAS
AF:
0.596
Gnomad FIN
AF:
0.347
Gnomad MID
AF:
0.331
Gnomad NFE
AF:
0.332
Gnomad OTH
AF:
0.417
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.426
AC:
64731
AN:
152020
Hom.:
15323
Cov.:
32
AF XY:
0.434
AC XY:
32237
AN XY:
74276
show subpopulations
African (AFR)
AF:
0.489
AC:
20294
AN:
41468
American (AMR)
AF:
0.537
AC:
8211
AN:
15280
Ashkenazi Jewish (ASJ)
AF:
0.283
AC:
981
AN:
3468
East Asian (EAS)
AF:
0.922
AC:
4753
AN:
5156
South Asian (SAS)
AF:
0.596
AC:
2870
AN:
4812
European-Finnish (FIN)
AF:
0.347
AC:
3664
AN:
10560
Middle Eastern (MID)
AF:
0.339
AC:
99
AN:
292
European-Non Finnish (NFE)
AF:
0.332
AC:
22536
AN:
67968
Other (OTH)
AF:
0.416
AC:
877
AN:
2106
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1724
3448
5173
6897
8621
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
602
1204
1806
2408
3010
<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:
0.404
Hom.:
2308
Bravo
AF:
0.443
Asia WGS
AF:
0.751
AC:
2609
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
0.077
DANN
Benign
0.65
PhyloP100
-2.2
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: rs9834312; hg19: chr3-58082709; API