chr2-182859220-G-A

Position:

• chr2-182859220-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001463.4(FRZB):​c.479-387C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 151,734 control chromosomes in the GnomAD database, including 36,575 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.69 (36575 hom., cov: 31)
• Consequence: FRZB NM_001463.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.358

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRZB	NM_001463.4	c.479-387C>T		intron_variant		ENST00000295113.5	NP_001454.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRZB	ENST00000295113.5	c.479-387C>T		intron_variant		1	NM_001463.4	ENSP00000295113	P1

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104610 AN: 151618 Hom.: 36533 Cov.: 31

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.713

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.684

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.690 AC: 104706 AN: 151734 Hom.: 36575 Cov.: 31 AF XY: 0.682 AC XY: 50516 AN XY: 74124

Gnomad4 AFR AF: 0.774

Gnomad4 AMR AF: 0.659

Gnomad4 ASJ AF: 0.736

Gnomad4 EAS AF: 0.515

Gnomad4 SAS AF: 0.539

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.679

Gnomad4 OTH AF: 0.682

Alfa AF: 0.682 Hom.: 57192

Bravo AF: 0.700

Asia WGS AF: 0.547 AC: 1901 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.7
DANN	Benign	0.35

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: rs6433993; hg19: chr2-183723948;