NM_006486.3:c.113C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006486.3(FBLN1):​c.113C>G​(p.Ala38Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A38V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

FBLN1
NM_006486.3 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.22
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19178501).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FBLN1NM_006486.3 linkc.113C>G p.Ala38Gly missense_variant Exon 2 of 17 ENST00000327858.11 NP_006477.3 P23142-1Q8NBH6
FBLN1NM_001996.4 linkc.113C>G p.Ala38Gly missense_variant Exon 2 of 15 NP_001987.3 P23142-4A0A8S0LWY1
FBLN1NM_006485.4 linkc.113C>G p.Ala38Gly missense_variant Exon 2 of 15 NP_006476.3 P23142-3Q8NBH6
FBLN1NM_006487.3 linkc.113C>G p.Ala38Gly missense_variant Exon 2 of 15 NP_006478.3 P23142-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FBLN1ENST00000327858.11 linkc.113C>G p.Ala38Gly missense_variant Exon 2 of 17 1 NM_006486.3 ENSP00000331544.6 P23142-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1458854
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
725368
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Uncertain
0.015
T
BayesDel_noAF
Benign
-0.22
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.088
T;T;.;.;T;.;.
Eigen
Benign
-0.38
Eigen_PC
Benign
-0.35
FATHMM_MKL
Benign
0.39
N
LIST_S2
Benign
0.84
T;T;T;T;T;T;T
M_CAP
Benign
0.062
D
MetaRNN
Benign
0.19
T;T;T;T;T;T;T
MetaSVM
Benign
-0.54
T
MutationAssessor
Benign
1.4
.;.;.;L;L;L;L
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-2.0
N;N;N;N;N;N;N
REVEL
Benign
0.073
Sift
Benign
0.10
T;T;T;T;T;T;T
Sift4G
Benign
0.13
T;T;T;T;T;T;T
Polyphen
0.71, 0.56, 0.73
.;.;P;P;P;.;.
Vest4
0.23, 0.24, 0.21
MutPred
0.53
.;Loss of stability (P = 0.0268);Loss of stability (P = 0.0268);Loss of stability (P = 0.0268);Loss of stability (P = 0.0268);Loss of stability (P = 0.0268);Loss of stability (P = 0.0268);
MVP
0.71
MPC
1.2
ClinPred
0.52
D
GERP RS
3.6
Varity_R
0.070
gMVP
0.39

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: rs202203586; hg19: chr22-45914595; API