2-182838608-G-A
Position:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_001463.4(FRZB):c.598C>T(p.Arg200Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,609,516 control chromosomes in the GnomAD database, including 9,796 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign,risk factor (no stars).
Frequency
Genomes: 𝑓 0.082 ( 755 hom., cov: 32)
Exomes 𝑓: 0.10 ( 9041 hom. )
Consequence
FRZB
NM_001463.4 missense
NM_001463.4 missense
Scores
3
9
6
Clinical Significance
Conservation
PhyloP100: 2.31
Genes affected
FRZB (HGNC:3959): (frizzled related protein) The protein encoded by this gene is a secreted protein that is involved in the regulation of bone development. Defects in this gene are a cause of female-specific osteoarthritis (OA) susceptibility. [provided by RefSeq, Apr 2010]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0022199154).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FRZB | NM_001463.4 | c.598C>T | p.Arg200Trp | missense_variant | 4/6 | ENST00000295113.5 | NP_001454.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FRZB | ENST00000295113.5 | c.598C>T | p.Arg200Trp | missense_variant | 4/6 | 1 | NM_001463.4 | ENSP00000295113.4 |
Frequencies
GnomAD3 genomes AF: 0.0818 AC: 12411AN: 151750Hom.: 755 Cov.: 32
GnomAD3 genomes
AF:
AC:
12411
AN:
151750
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:
GnomAD3 exomes AF: 0.0818 AC: 20449AN: 249838Hom.: 1128 AF XY: 0.0840 AC XY: 11338AN XY: 135032
GnomAD3 exomes
AF:
AC:
20449
AN:
249838
Hom.:
AF XY:
AC XY:
11338
AN XY:
135032
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.104 AC: 151565AN: 1457648Hom.: 9041 Cov.: 31 AF XY: 0.103 AC XY: 74509AN XY: 725312
GnomAD4 exome
AF:
AC:
151565
AN:
1457648
Hom.:
Cov.:
31
AF XY:
AC XY:
74509
AN XY:
725312
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0817 AC: 12405AN: 151868Hom.: 755 Cov.: 32 AF XY: 0.0783 AC XY: 5811AN XY: 74218
GnomAD4 genome
AF:
AC:
12405
AN:
151868
Hom.:
Cov.:
32
AF XY:
AC XY:
5811
AN XY:
74218
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
440
ALSPAC
AF:
AC:
486
ESP6500AA
AF:
AC:
149
ESP6500EA
AF:
AC:
1007
ExAC
AF:
AC:
9896
Asia WGS
AF:
AC:
72
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign; risk factor
Submissions summary: Benign:1Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
FRZB-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 08, 2024 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Osteoarthritis susceptibility 1 Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Jun 29, 2004 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MPC
ClinPred
T
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