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GeneBe

22-45503057-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_006486.3(FBLN1):c.72G>A(p.Ala24=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00209 in 1,247,188 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0093 ( 20 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 6 hom. )

Consequence

FBLN1
NM_006486.3 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.110
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 -19 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 22-45503057-G-A is Benign according to our data. Variant chr22-45503057-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 193340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.11 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0093 (1413/151854) while in subpopulation AFR AF= 0.0315 (1306/41500). AF 95% confidence interval is 0.0301. There are 20 homozygotes in gnomad4. There are 667 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1410 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FBLN1NM_006486.3 linkuse as main transcriptc.72G>A p.Ala24= synonymous_variant 1/17 ENST00000327858.11
FBLN1NM_001996.4 linkuse as main transcriptc.72G>A p.Ala24= synonymous_variant 1/15
FBLN1NM_006485.4 linkuse as main transcriptc.72G>A p.Ala24= synonymous_variant 1/15
FBLN1NM_006487.3 linkuse as main transcriptc.72G>A p.Ala24= synonymous_variant 1/15

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FBLN1ENST00000327858.11 linkuse as main transcriptc.72G>A p.Ala24= synonymous_variant 1/171 NM_006486.3 P1P23142-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00929
AC:
1410
AN:
151746
Hom.:
20
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0315
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00322
Gnomad ASJ
AF:
0.00694
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000295
Gnomad OTH
AF:
0.00623
GnomAD3 exomes
AF:
0.00197
AC:
19
AN:
9648
Hom.:
0
AF XY:
0.00132
AC XY:
8
AN XY:
6074
show subpopulations
Gnomad AFR exome
AF:
0.0366
Gnomad AMR exome
AF:
0.00229
Gnomad ASJ exome
AF:
0.00703
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000509
Gnomad OTH exome
AF:
0.00633
GnomAD4 exome
AF:
0.00109
AC:
1194
AN:
1095334
Hom.:
6
Cov.:
30
AF XY:
0.00104
AC XY:
544
AN XY:
522814
show subpopulations
Gnomad4 AFR exome
AF:
0.0305
Gnomad4 AMR exome
AF:
0.00315
Gnomad4 ASJ exome
AF:
0.00855
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000159
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000210
Gnomad4 OTH exome
AF:
0.00293
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00930
AC:
1413
AN:
151854
Hom.:
20
Cov.:
32
AF XY:
0.00899
AC XY:
667
AN XY:
74228
show subpopulations
Gnomad4 AFR
AF:
0.0315
Gnomad4 AMR
AF:
0.00321
Gnomad4 ASJ
AF:
0.00694
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000295
Gnomad4 OTH
AF:
0.00616
Alfa
AF:
0.00555
Hom.:
0
Bravo
AF:
0.0104
Asia WGS
AF:
0.00291
AC:
10
AN:
3446

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Feb 27, 2015- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeOct 05, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.39
Cadd
Benign
12
Dann
Benign
0.97
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.0

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: rs559662894; hg19: chr22-45898937; API