Variant 2-182834921-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001463.4(FRZB):c.906T>C(p.Asp302Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00947 in 1,613,182 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0060 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0098 ( 92 hom. )

Consequence

FRZB
NM_001463.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.572

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 2-182834921-A-G is Benign according to our data. Variant chr2-182834921-A-G is described in ClinVar as [Benign]. Clinvar id is 774292.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.572 with no splicing effect.

BS2

High AC in GnomAd4 at 912 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRZB	NM_001463.4 linkuse as main transcript	c.906T>C	p.Asp302Asp	synonymous_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.906T>C	p.Asp302Asp	synonymous_variant	6/6	1	NM_001463.4	ENSP00000295113.4		Q92765

Frequencies

GnomAD3 genomes

AF:

0.00600

AC:

912

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00217

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00452

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0106

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00628

AC:

1576

AN:

250782

Hom.:

AF XY:

0.00612

AC XY:

829

AN XY:

135526

show subpopulations

Gnomad AFR exome

AF:

0.00172

Gnomad AMR exome

AF:

0.00212

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000621

Gnomad FIN exome

AF:

0.00615

Gnomad NFE exome

AF:

0.0112

Gnomad OTH exome

AF:

0.00508

GnomAD4 exome

AF:

0.00983

AC:

14365

AN:

1460996

Hom.:

Cov.:

AF XY:

0.00944

AC XY:

6863

AN XY:

726798

show subpopulations

Gnomad4 AFR exome

AF:

0.00185

Gnomad4 AMR exome

AF:

0.00226

Gnomad4 ASJ exome

AF:

0.00180

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000417

Gnomad4 FIN exome

AF:

0.00669

Gnomad4 NFE exome

AF:

0.0120

Gnomad4 OTH exome

AF:

0.00719

GnomAD4 genome

AF:

0.00599

AC:

912

AN:

152186

Hom.:

Cov.:

AF XY:

0.00539

AC XY:

401

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.00217

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00452

Gnomad4 NFE

AF:

0.0106

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00870

Hom.:

Bravo

AF:

0.00603

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00977

EpiControl

AF:

0.00901

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 20, 2018	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	FRZB: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.7

DANN

Benign

0.44

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