rs288323

Variant names:

• chr2-182836173-T-C
• rs288323
• NM_001463.4:c.862-1208A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001463.4(FRZB):​c.862-1208A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0544 in 152,148 control chromosomes in the GnomAD database, including 377 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 0.054 (377 hom., cov: 32)
• Consequence: FRZB NM_001463.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.556
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRZB	NM_001463.4	c.862-1208A>G		intron_variant	Intron 5 of 5	ENST00000295113.5	NP_001454.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRZB	ENST00000295113.5	c.862-1208A>G		intron_variant	Intron 5 of 5	1	NM_001463.4	ENSP00000295113.4

Frequencies

GnomAD3 genomes AF: 0.0542 AC: 8246 AN: 152030 Hom.: 371 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0422

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00705

Gnomad FIN AF: 0.00781

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0362

Gnomad OTH AF: 0.0585

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

GnomAD4 genome AF: 0.0544 AC: 8281 AN: 152148 Hom.: 377 Cov.: 32 AF XY: 0.0523 AC XY: 3889 AN XY: 74388

African (AFR) AF: 0.117 AC: 4841 AN: 41512

American (AMR) AF: 0.0421 AC: 643 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0228 AC: 79 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00684 AC: 33 AN: 4822

European-Finnish (FIN) AF: 0.00781 AC: 83 AN: 10624

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0362 AC: 2463 AN: 67980

Other (OTH) AF: 0.0579 AC: 122 AN: 2108

Alfa AF: 0.0431 Hom.: 202

Bravo AF: 0.0599

Asia WGS AF: 0.0120 AC: 42 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.3
DANN	Benign	0.90
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs288323; hg19: chr2-183700901;