chr2-182836860-A-G

Variant names:

• chr2-182836860-A-G
• rs288324
• NM_001463.4:c.861+1088T>C

Variant summary

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

The NM_001463.4(FRZB):​c.861+1088T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 151,756 control chromosomes in the GnomAD database, including 21,254 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 0.52 (21254 hom., cov: 31)
• Consequence: FRZB NM_001463.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001463.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRZB	NM_001463.4	MANE Select	c.861+1088T>C		intron	N/A	NP_001454.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRZB	ENST00000295113.5	TSL:1 MANE Select	c.861+1088T>C		intron	N/A	ENSP00000295113.4	Q92765
	FRZB	ENST00000957773.1		c.888+144T>C		intron	N/A	ENSP00000627832.1
	FRZB	ENST00000888346.1		c.813+1088T>C		intron	N/A	ENSP00000558405.1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78797 AN: 151638 Hom.: 21223 Cov.: 31

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.713

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.520 AC: 78887 AN: 151756 Hom.: 21254 Cov.: 31 AF XY: 0.519 AC XY: 38487 AN XY: 74184

African (AFR) AF: 0.646 AC: 26733 AN: 41404

American (AMR) AF: 0.404 AC: 6149 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1381 AN: 3468

East Asian (EAS) AF: 0.598 AC: 3072 AN: 5134

South Asian (SAS) AF: 0.574 AC: 2760 AN: 4810

European-Finnish (FIN) AF: 0.483 AC: 5093 AN: 10550

Middle Eastern (MID) AF: 0.397 AC: 116 AN: 292

European-Non Finnish (NFE) AF: 0.470 AC: 31896 AN: 67852

Other (OTH) AF: 0.491 AC: 1038 AN: 2112

Alfa AF: 0.482 Hom.: 31355

Bravo AF: 0.520

Asia WGS AF: 0.601 AC: 2090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.55
DANN	Benign	0.34
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs288324; hg19: chr2-183701588;