2-182834921-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001463.4(FRZB):c.906T>C(p.Asp302=) 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.572

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]

ACMG classification

Verdict is Benign. Variant got -11 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_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.572 with no splicing effect.
• BS2: High AC in GnomAd at 912 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRZB	NM_001463.4	c.906T>C	p.Asp302=	synonymous_variant	6/6	ENST00000295113.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRZB	ENST00000295113.5	c.906T>C	p.Asp302=	synonymous_variant	6/6	1	NM_001463.4	P1

Frequencies

GnomAD3 genomes AF: 0.00600 AC: 912 AN: 152068 Hom.: 2 Cov.: 32

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.: 11 AF XY: 0.00612 AC XY: 829 AN XY: 135526

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.: 92 Cov.: 30 AF XY: 0.00944 AC XY: 6863 AN XY: 726798

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.: 2 Cov.: 32 AF XY: 0.00539 AC XY: 401 AN XY: 74404

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.: 3

Bravo AF: 0.00603

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00977

EpiControl AF: 0.00901

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 20, 2018

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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

Other links and lift over

dbSNP: rs41270213; hg19: chr2-183699648; COSMIC: COSV99717564;