2-162174951-C-G
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4
The NM_004460.5(FAP):c.1885G>C(p.Val629Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,611,696 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts 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. V629I) has been classified as Uncertain significance.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000027 ( 1 hom. )
Consequence
FAP
NM_004460.5 missense
NM_004460.5 missense
Scores
8
11
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 3.79
Publications
1 publications found
Genes affected
FAP (HGNC:3590): (fibroblast activation protein alpha) The protein encoded by this gene is a homodimeric integral membrane gelatinase belonging to the serine protease family. It is selectively expressed in reactive stromal fibroblasts of epithelial cancers, granulation tissue of healing wounds, and malignant cells of bone and soft tissue sarcomas. This protein is thought to be involved in the control of fibroblast growth or epithelial-mesenchymal interactions during development, tissue repair, and epithelial carcinogenesis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2014]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.36717778).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| FAP | NM_004460.5 | c.1885G>C | p.Val629Leu | missense_variant | Exon 22 of 26 | ENST00000188790.9 | NP_004451.2 | |
| FAP | NM_001291807.3 | c.1810G>C | p.Val604Leu | missense_variant | Exon 21 of 25 | NP_001278736.1 | ||
| FAP | XM_011510796.4 | c.1855G>C | p.Val619Leu | missense_variant | Exon 21 of 25 | XP_011509098.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.00000658 AC: 1AN: 152036Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152036
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1459660Hom.: 1 Cov.: 29 AF XY: 0.00000413 AC XY: 3AN XY: 726220 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
4
AN:
1459660
Hom.:
Cov.:
29
AF XY:
AC XY:
3
AN XY:
726220
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33382
American (AMR)
AF:
AC:
0
AN:
44672
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26044
East Asian (EAS)
AF:
AC:
3
AN:
39656
South Asian (SAS)
AF:
AC:
0
AN:
86214
European-Finnish (FIN)
AF:
AC:
0
AN:
53366
Middle Eastern (MID)
AF:
AC:
0
AN:
5752
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1110312
Other (OTH)
AF:
AC:
0
AN:
60262
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.400
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000658 AC: 1AN: 152036Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74258 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152036
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74258
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41408
American (AMR)
AF:
AC:
0
AN:
15260
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
1
AN:
5184
South Asian (SAS)
AF:
AC:
0
AN:
4820
European-Finnish (FIN)
AF:
AC:
0
AN:
10586
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67996
Other (OTH)
AF:
AC:
0
AN:
2084
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;.
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Uncertain
.;N;N
REVEL
Benign
Sift
Uncertain
.;D;D
Sift4G
Uncertain
D;D;T
Polyphen
0.0060, 0.013
.;B;B
Vest4
MutPred
0.62
.;Loss of helix (P = 0.0104);.;
MVP
MPC
0.12
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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