22-45518795-T-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006486.3(FBLN1):​c.185+8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,597,416 control chromosomes in the GnomAD database, including 13,408 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 4603 hom., cov: 32)
Exomes 𝑓: 0.093 ( 8805 hom. )

Consequence

FBLN1
NM_006486.3 splice_region, intron

Scores

2
Splicing: ADA: 0.00008021
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.213
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
Variant 22-45518795-T-C is Benign according to our data. Variant chr22-45518795-T-C is described in ClinVar as [Benign]. Clinvar id is 1286401.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FBLN1NM_006486.3 linkc.185+8T>C splice_region_variant, intron_variant Intron 2 of 16 ENST00000327858.11 NP_006477.3 P23142-1Q8NBH6
FBLN1NM_001996.4 linkc.185+8T>C splice_region_variant, intron_variant Intron 2 of 14 NP_001987.3 P23142-4A0A8S0LWY1
FBLN1NM_006485.4 linkc.185+8T>C splice_region_variant, intron_variant Intron 2 of 14 NP_006476.3 P23142-3Q8NBH6
FBLN1NM_006487.3 linkc.185+8T>C splice_region_variant, intron_variant Intron 2 of 14 NP_006478.3 P23142-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FBLN1ENST00000327858.11 linkc.185+8T>C splice_region_variant, intron_variant Intron 2 of 16 1 NM_006486.3 ENSP00000331544.6 P23142-1

Frequencies

GnomAD3 genomes
AF:
0.184
AC:
27925
AN:
152116
Hom.:
4583
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.445
Gnomad AMI
AF:
0.0440
Gnomad AMR
AF:
0.0882
Gnomad ASJ
AF:
0.0718
Gnomad EAS
AF:
0.0510
Gnomad SAS
AF:
0.0671
Gnomad FIN
AF:
0.116
Gnomad MID
AF:
0.0348
Gnomad NFE
AF:
0.0845
Gnomad OTH
AF:
0.135
GnomAD2 exomes
AF:
0.0981
AC:
22276
AN:
226968
AF XY:
0.0907
show subpopulations
Gnomad AFR exome
AF:
0.447
Gnomad AMR exome
AF:
0.0521
Gnomad ASJ exome
AF:
0.0679
Gnomad EAS exome
AF:
0.0393
Gnomad FIN exome
AF:
0.115
Gnomad NFE exome
AF:
0.0838
Gnomad OTH exome
AF:
0.0770
GnomAD4 exome
AF:
0.0933
AC:
134869
AN:
1445182
Hom.:
8805
Cov.:
30
AF XY:
0.0908
AC XY:
65207
AN XY:
717998
show subpopulations
Gnomad4 AFR exome
AF:
0.452
AC:
14935
AN:
33056
Gnomad4 AMR exome
AF:
0.0562
AC:
2420
AN:
43060
Gnomad4 ASJ exome
AF:
0.0671
AC:
1732
AN:
25812
Gnomad4 EAS exome
AF:
0.0639
AC:
2492
AN:
39004
Gnomad4 SAS exome
AF:
0.0640
AC:
5357
AN:
83712
Gnomad4 FIN exome
AF:
0.112
AC:
5879
AN:
52650
Gnomad4 NFE exome
AF:
0.0869
AC:
95791
AN:
1102336
Gnomad4 Remaining exome
AF:
0.0996
AC:
5955
AN:
59794
Heterozygous variant carriers
0
5879
11758
17638
23517
29396
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
3766
7532
11298
15064
18830
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.184
AC:
28001
AN:
152234
Hom.:
4603
Cov.:
32
AF XY:
0.180
AC XY:
13382
AN XY:
74436
show subpopulations
Gnomad4 AFR
AF:
0.446
AC:
0.44558
AN:
0.44558
Gnomad4 AMR
AF:
0.0881
AC:
0.0880585
AN:
0.0880585
Gnomad4 ASJ
AF:
0.0718
AC:
0.0717579
AN:
0.0717579
Gnomad4 EAS
AF:
0.0510
AC:
0.0509653
AN:
0.0509653
Gnomad4 SAS
AF:
0.0671
AC:
0.0671363
AN:
0.0671363
Gnomad4 FIN
AF:
0.116
AC:
0.116189
AN:
0.116189
Gnomad4 NFE
AF:
0.0845
AC:
0.0844897
AN:
0.0844897
Gnomad4 OTH
AF:
0.140
AC:
0.13981
AN:
0.13981
Heterozygous variant carriers
0
993
1986
2980
3973
4966
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
264
528
792
1056
1320
<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:
0.123
Hom.:
1433
Bravo
AF:
0.192
Asia WGS
AF:
0.100
AC:
347
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Jan 27, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

May 12, 2021
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.70
CADD
Benign
6.1
DANN
Benign
0.88
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000080
dbscSNV1_RF
Benign
0.070
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs78488153; hg19: chr22-45914675; API