Variant 2-182834857-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001463.4(FRZB):c.970C>G(p.Arg324Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0858 in 1,610,096 control chromosomes in the GnomAD database, including 8,175 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.13 ( 2120 hom., cov: 32)

Exomes 𝑓: 0.081 ( 6055 hom. )

Consequence

FRZB
NM_001463.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.92

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013847649).

BP6

Variant 2-182834857-G-C is Benign according to our data. Variant chr2-182834857-G-C is described in ClinVar as [Benign]. Clinvar id is 5220.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 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.970C>G	p.Arg324Gly	missense_variant	6/6	ENST00000295113.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRZB	ENST00000295113.5 linkuse as main transcript	c.970C>G	p.Arg324Gly	missense_variant	6/6	1	NM_001463.4	P1

Frequencies

GnomAD3 genomes

AF:

0.133

AC:

20160

AN:

151988

Hom.:

2119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.288

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0903

Gnomad ASJ

AF:

0.0982

Gnomad EAS

AF:

0.00984

Gnomad SAS

AF:

0.0597

Gnomad FIN

AF:

0.0209

Gnomad MID

AF:

0.143

Gnomad NFE

AF:

0.0826

Gnomad OTH

AF:

0.133

GnomAD3 exomes

AF:

0.0801

AC:

20106

AN:

250924

Hom.:

1335

AF XY:

0.0765

AC XY:

10376

AN XY:

135600

show subpopulations

Gnomad AFR exome

AF:

0.292

Gnomad AMR exome

AF:

0.0607

Gnomad ASJ exome

AF:

0.0927

Gnomad EAS exome

AF:

0.00756

Gnomad SAS exome

AF:

0.0574

Gnomad FIN exome

AF:

0.0259

Gnomad NFE exome

AF:

0.0822

Gnomad OTH exome

AF:

0.0922

GnomAD4 exome

AF:

0.0809

AC:

117951

AN:

1457990

Hom.:

6055

Cov.:

AF XY:

0.0794

AC XY:

57582

AN XY:

725508

show subpopulations

Gnomad4 AFR exome

AF:

0.292

Gnomad4 AMR exome

AF:

0.0651

Gnomad4 ASJ exome

AF:

0.0936

Gnomad4 EAS exome

AF:

0.00491

Gnomad4 SAS exome

AF:

0.0573

Gnomad4 FIN exome

AF:

0.0276

Gnomad4 NFE exome

AF:

0.0814

Gnomad4 OTH exome

AF:

0.0884

GnomAD4 genome

AF:

0.133

AC:

20184

AN:

152106

Hom.:

2120

Cov.:

AF XY:

0.127

AC XY:

9465

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.288

Gnomad4 AMR

AF:

0.0901

Gnomad4 ASJ

AF:

0.0982

Gnomad4 EAS

AF:

0.00948

Gnomad4 SAS

AF:

0.0595

Gnomad4 FIN

AF:

0.0209

Gnomad4 NFE

AF:

0.0826

Gnomad4 OTH

AF:

0.134

Alfa

AF:

0.0461

Hom.:

Bravo

AF:

0.145

TwinsUK

AF:

0.0763

AC:

283

ALSPAC

AF:

0.0823

AC:

317

ESP6500AA

AF:

0.284

AC:

1250

ESP6500EA

AF:

0.0880

AC:

757

ExAC

AF:

0.0858

AC:

10413

Asia WGS

AF:

0.0680

AC:

239

AN:

3478

EpiCase

AF:

0.0918

EpiControl

AF:

0.0946

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 03, 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

Benign

0.13

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.22

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Benign

-0.13

Eigen_PC

Benign

0.025

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.58

MetaRNN

Benign

0.0014

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

MutationTaster

Benign

0.012

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.75

REVEL

Benign

0.24

Sift

Uncertain

0.012

Sift4G

Benign

0.099

Polyphen

0.11

Vest4

0.051

MPC

0.58

ClinPred

0.014

GERP RS

3.6

Varity_R

0.12

gMVP

0.47

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.

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