22-45563660-G-A

Variant summary

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

The NM_006486.3(FBLN1):​c.1698-10851G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,112 control chromosomes in the GnomAD database, including 41,923 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 0.74 ( 41923 hom., cov: 32)

Consequence

FBLN1
NM_006486.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.95

Publications

7 publications found
Variant links:
Genes affected
FBLN1 (HGNC:3600): (fibulin 1) Fibulin 1 is a secreted glycoprotein that becomes incorporated into a fibrillar extracellular matrix. Calcium-binding is apparently required to mediate its binding to laminin and nidogen. It mediates platelet adhesion via binding fibrinogen. Four splice variants which differ in the 3' end have been identified. Each variant encodes a different isoform, but no functional distinctions have been identified among the four variants. [provided by RefSeq, Jul 2008]
FBLN1 Gene-Disease associations (from GenCC):
  • FBLN1-related developmental delay-central nervous system anomaly-syndactyly syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • synpolydactyly type 2
    Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P

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=-1.03).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FBLN1NM_006486.3 linkc.1698-10851G>A intron_variant Intron 14 of 16 ENST00000327858.11 NP_006477.3 P23142-1Q8NBH6
FBLN1NM_006485.4 linkc.1698-1224G>A intron_variant Intron 14 of 14 NP_006476.3 P23142-3Q8NBH6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FBLN1ENST00000327858.11 linkc.1698-10851G>A intron_variant Intron 14 of 16 1 NM_006486.3 ENSP00000331544.6 P23142-1
FBLN1ENST00000442170.6 linkc.1698-1224G>A intron_variant Intron 14 of 14 1 ENSP00000393812.2 P23142-3

Frequencies

GnomAD3 genomes
AF:
0.741
AC:
112608
AN:
151994
Hom.:
41891
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.822
Gnomad AMI
AF:
0.758
Gnomad AMR
AF:
0.671
Gnomad ASJ
AF:
0.725
Gnomad EAS
AF:
0.659
Gnomad SAS
AF:
0.694
Gnomad FIN
AF:
0.751
Gnomad MID
AF:
0.801
Gnomad NFE
AF:
0.716
Gnomad OTH
AF:
0.736
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.741
AC:
112686
AN:
152112
Hom.:
41923
Cov.:
32
AF XY:
0.741
AC XY:
55132
AN XY:
74358
show subpopulations
African (AFR)
AF:
0.822
AC:
34105
AN:
41510
American (AMR)
AF:
0.670
AC:
10247
AN:
15292
Ashkenazi Jewish (ASJ)
AF:
0.725
AC:
2517
AN:
3472
East Asian (EAS)
AF:
0.660
AC:
3402
AN:
5156
South Asian (SAS)
AF:
0.694
AC:
3339
AN:
4814
European-Finnish (FIN)
AF:
0.751
AC:
7957
AN:
10602
Middle Eastern (MID)
AF:
0.806
AC:
237
AN:
294
European-Non Finnish (NFE)
AF:
0.716
AC:
48644
AN:
67950
Other (OTH)
AF:
0.733
AC:
1547
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
1506
3011
4517
6022
7528
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
850
1700
2550
3400
4250
<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:
0.723
Hom.:
119310
Bravo
AF:
0.740
Asia WGS
AF:
0.642
AC:
2234
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.0030
DANN
Benign
0.54
PhyloP100
-2.9
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: rs743931; hg19: chr22-45959540; API