22-45541269-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006486.3(FBLN1):​c.963C>T​(p.Ile321Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 1,613,910 control chromosomes in the GnomAD database, including 126,079 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10329 hom., cov: 34)
Exomes 𝑓: 0.39 ( 115750 hom. )

Consequence

FBLN1
NM_006486.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.24
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 made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
Variant 22-45541269-C-T is Benign according to our data. Variant chr22-45541269-C-T is described in ClinVar as [Benign]. Clinvar id is 1232901.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-45541269-C-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-2.24 with no splicing effect.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FBLN1NM_006486.3 linkc.963C>T p.Ile321Ile synonymous_variant Exon 9 of 17 ENST00000327858.11 NP_006477.3 P23142-1Q8NBH6
FBLN1NM_001996.4 linkc.963C>T p.Ile321Ile synonymous_variant Exon 9 of 15 NP_001987.3 P23142-4A0A8S0LWY1
FBLN1NM_006485.4 linkc.963C>T p.Ile321Ile synonymous_variant Exon 9 of 15 NP_006476.3 P23142-3Q8NBH6
FBLN1NM_006487.3 linkc.963C>T p.Ile321Ile synonymous_variant Exon 9 of 15 NP_006478.3 P23142-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FBLN1ENST00000327858.11 linkc.963C>T p.Ile321Ile synonymous_variant Exon 9 of 17 1 NM_006486.3 ENSP00000331544.6 P23142-1

Frequencies

GnomAD3 genomes
AF:
0.356
AC:
54085
AN:
152040
Hom.:
10333
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.242
Gnomad AMI
AF:
0.655
Gnomad AMR
AF:
0.331
Gnomad ASJ
AF:
0.412
Gnomad EAS
AF:
0.177
Gnomad SAS
AF:
0.287
Gnomad FIN
AF:
0.490
Gnomad MID
AF:
0.503
Gnomad NFE
AF:
0.421
Gnomad OTH
AF:
0.360
GnomAD3 exomes
AF:
0.358
AC:
90055
AN:
251468
Hom.:
17578
AF XY:
0.366
AC XY:
49676
AN XY:
135912
show subpopulations
Gnomad AFR exome
AF:
0.237
Gnomad AMR exome
AF:
0.243
Gnomad ASJ exome
AF:
0.419
Gnomad EAS exome
AF:
0.178
Gnomad SAS exome
AF:
0.297
Gnomad FIN exome
AF:
0.486
Gnomad NFE exome
AF:
0.425
Gnomad OTH exome
AF:
0.385
GnomAD4 exome
AF:
0.392
AC:
573066
AN:
1461750
Hom.:
115750
Cov.:
49
AF XY:
0.392
AC XY:
285268
AN XY:
727190
show subpopulations
Gnomad4 AFR exome
AF:
0.233
Gnomad4 AMR exome
AF:
0.256
Gnomad4 ASJ exome
AF:
0.414
Gnomad4 EAS exome
AF:
0.178
Gnomad4 SAS exome
AF:
0.305
Gnomad4 FIN exome
AF:
0.478
Gnomad4 NFE exome
AF:
0.412
Gnomad4 OTH exome
AF:
0.384
GnomAD4 genome
AF:
0.355
AC:
54076
AN:
152160
Hom.:
10329
Cov.:
34
AF XY:
0.357
AC XY:
26555
AN XY:
74390
show subpopulations
Gnomad4 AFR
AF:
0.241
Gnomad4 AMR
AF:
0.331
Gnomad4 ASJ
AF:
0.412
Gnomad4 EAS
AF:
0.177
Gnomad4 SAS
AF:
0.286
Gnomad4 FIN
AF:
0.490
Gnomad4 NFE
AF:
0.421
Gnomad4 OTH
AF:
0.355
Alfa
AF:
0.397
Hom.:
24645
Bravo
AF:
0.338
Asia WGS
AF:
0.203
AC:
706
AN:
3478
EpiCase
AF:
0.426
EpiControl
AF:
0.425

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
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

- -

Nov 11, 2018
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Synpolydactyly type 2 Benign:1
Aug 10, 2021
Genome-Nilou Lab
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
0.21
DANN
Benign
0.64
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6

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

LitVar

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

Other links and lift over

dbSNP: rs9682; hg19: chr22-45937149; COSMIC: COSV53043913; API