Variant 2-182838608-G-A details in Genebe, Genetics Data Aggregator

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 (★).

Frequency

Genomes: 𝑓 0.082 ( 755 hom., cov: 32)

Exomes 𝑓: 0.10 ( 9041 hom. )

Consequence

FRZB
NM_001463.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 2.31

Variant links:

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]

FRZB links:

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	UniProt
FRZB	NM_001463.4 linkuse as main transcript	c.598C>T	p.Arg200Trp	missense_variant	4/6	ENST00000295113.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRZB	ENST00000295113.5 linkuse as main transcript	c.598C>T	p.Arg200Trp	missense_variant	4/6	1	NM_001463.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0818

AC:

12411

AN:

151750

Hom.:

755

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0306

Gnomad AMI

AF:

0.387

Gnomad AMR

AF:

0.0847

Gnomad ASJ

AF:

0.161

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0336

Gnomad FIN

AF:

0.0513

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.118

Gnomad OTH

AF:

0.0886

GnomAD3 exomes

AF:

0.0818

AC:

20449

AN:

249838

Hom.:

1128

AF XY:

0.0840

AC XY:

11338

AN XY:

135032

show subpopulations

Gnomad AFR exome

AF:

0.0272

Gnomad AMR exome

AF:

0.0564

Gnomad ASJ exome

AF:

0.158

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0366

Gnomad FIN exome

AF:

0.0520

Gnomad NFE exome

AF:

0.122

Gnomad OTH exome

AF:

0.0928

GnomAD4 exome

AF:

0.104

AC:

151565

AN:

1457648

Hom.:

9041

Cov.:

AF XY:

0.103

AC XY:

74509

AN XY:

725312

show subpopulations

Gnomad4 AFR exome

AF:

0.0248

Gnomad4 AMR exome

AF:

0.0585

Gnomad4 ASJ exome

AF:

0.159

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0392

Gnomad4 FIN exome

AF:

0.0569

Gnomad4 NFE exome

AF:

0.118

Gnomad4 OTH exome

AF:

0.0956

GnomAD4 genome

AF:

0.0817

AC:

12405

AN:

151868

Hom.:

755

Cov.:

AF XY:

0.0783

AC XY:

5811

AN XY:

74218

show subpopulations

Gnomad4 AFR

AF:

0.0305

Gnomad4 AMR

AF:

0.0845

Gnomad4 ASJ

AF:

0.161

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0330

Gnomad4 FIN

AF:

0.0513

Gnomad4 NFE

AF:

0.118

Gnomad4 OTH

AF:

0.0877

Alfa

AF:

0.109

Hom.:

1815

Bravo

AF:

0.0828

TwinsUK

AF:

0.119

AC:

440

ALSPAC

AF:

0.126

AC:

486

ESP6500AA

AF:

0.0338

AC:

149

ESP6500EA

AF:

0.117

AC:

1007

ExAC

AF:

0.0815

AC:

9896

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.124

EpiControl

AF:

0.123

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

FRZB-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 11, 2019

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

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jun 29, 2004

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.70

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

0.070

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.42

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.98

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

2.1e-7

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.27

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.34

MPC

1.2

ClinPred

0.013

GERP RS

3.2

Varity_R

0.40

gMVP

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over