Variant chr2-182834955-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001463.4(FRZB):c.872T>C(p.Met291Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0068 in 1,609,976 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0058 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0069 ( 43 hom. )

Consequence

FRZB
NM_001463.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.54

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006691307).

BP6

Variant 2-182834955-A-G is Benign according to our data. Variant chr2-182834955-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 774293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 877 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRZB	NM_001463.4 linkuse as main transcript	c.872T>C	p.Met291Thr	missense_variant	6/6	ENST00000295113.5	NP_001454.2	Q92765D9ZGF6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRZB	ENST00000295113.5 linkuse as main transcript	c.872T>C	p.Met291Thr	missense_variant	6/6	1	NM_001463.4	ENSP00000295113.4		Q92765

Frequencies

GnomAD3 genomes

AF:

0.00577

AC:

877

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.00564

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00452

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00816

Gnomad OTH

AF:

0.00908

GnomAD3 exomes

AF:

0.00626

AC:

1571

AN:

250764

Hom.:

AF XY:

0.00607

AC XY:

823

AN XY:

135524

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00624

Gnomad ASJ exome

AF:

0.0183

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00518

Gnomad NFE exome

AF:

0.00884

Gnomad OTH exome

AF:

0.00540

GnomAD4 exome

AF:

0.00691

AC:

10069

AN:

1457752

Hom.:

Cov.:

AF XY:

0.00666

AC XY:

4834

AN XY:

725450

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.00594

Gnomad4 ASJ exome

AF:

0.0184

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00558

Gnomad4 NFE exome

AF:

0.00773

Gnomad4 OTH exome

AF:

0.00674

GnomAD4 genome

AF:

0.00576

AC:

877

AN:

152224

Hom.:

Cov.:

AF XY:

0.00531

AC XY:

395

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.00180

Gnomad4 AMR

AF:

0.00563

Gnomad4 ASJ

AF:

0.0164

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00452

Gnomad4 NFE

AF:

0.00816

Gnomad4 OTH

AF:

0.00899

Alfa

AF:

0.00741

Hom.:

Bravo

AF:

0.00581

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.00675

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.00733

AC:

ExAC

AF:

0.00628

AC:

762

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00819

EpiControl

AF:

0.00806

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2023	FRZB: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.24

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.62

MetaRNN

Benign

0.0067

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.91

REVEL

Benign

0.076

Sift

Benign

0.32

Sift4G

Benign

0.20

Polyphen

0.018

Vest4

0.090

MVP

0.90

MPC

0.55

ClinPred

0.024

GERP RS

4.4

Varity_R

0.12

gMVP

0.28

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