rs757979640

Variant summary

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

The NM_212482.4(FN1):ā€‹c.7401T>Gā€‹(p.Asp2467Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,652 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.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

FN1
NM_212482.4 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.873
Variant links:
Genes affected
FN1 (HGNC:3778): (fibronectin 1) This gene encodes fibronectin, a glycoprotein present in a soluble dimeric form in plasma, and in a dimeric or multimeric form at the cell surface and in extracellular matrix. The encoded preproprotein is proteolytically processed to generate the mature protein. Fibronectin is involved in cell adhesion and migration processes including embryogenesis, wound healing, blood coagulation, host defense, and metastasis. The gene has three regions subject to alternative splicing, with the potential to produce 20 different transcript variants, at least one of which encodes an isoform that undergoes proteolytic processing. The full-length nature of some variants has not been determined. [provided by RefSeq, Jan 2016]
ATIC (HGNC:794): (5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase) This gene encodes a bifunctional protein that catalyzes the last two steps of the de novo purine biosynthetic pathway. The N-terminal domain has phosphoribosylaminoimidazolecarboxamide formyltransferase activity, and the C-terminal domain has IMP cyclohydrolase activity. A mutation in this gene results in AICA-ribosiduria. [provided by RefSeq, Sep 2009]

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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=0.26087582).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FN1NM_212482.4 linkc.7401T>G p.Asp2467Glu missense_variant Exon 46 of 46 ENST00000354785.11 NP_997647.2 P02751-15Q6MZM7Q9UQS6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FN1ENST00000354785.11 linkc.7401T>G p.Asp2467Glu missense_variant Exon 46 of 46 1 NM_212482.4 ENSP00000346839.4 P02751-15

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460652
Hom.:
0
Cov.:
28
AF XY:
0.00000138
AC XY:
1
AN XY:
726744
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Benign
-0.031
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
14
DANN
Uncertain
0.99
DEOGEN2
Benign
0.40
.;.;.;.;.;T;.;.;.;.;T
Eigen
Benign
0.12
Eigen_PC
Benign
0.15
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Uncertain
0.95
D;D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.26
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.88
T
MutationAssessor
Benign
2.0
.;.;.;.;.;M;.;.;.;.;.
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-0.97
N;N;N;N;N;N;N;N;N;N;N
REVEL
Benign
0.078
Sift
Benign
0.21
T;T;T;D;T;T;T;T;D;T;T
Sift4G
Benign
0.48
T;T;T;T;T;T;T;T;T;T;T
Polyphen
1.0
D;B;D;P;B;D;.;D;B;D;.
Vest4
0.30
MutPred
0.40
.;.;.;.;.;Gain of disorder (P = 0.1185);.;.;.;.;.;
MVP
0.87
MPC
0.36
ClinPred
0.47
T
GERP RS
2.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.056
gMVP
0.21

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: rs757979640; hg19: chr2-216226311; API