rs4666865

Variant names:

• chr2-182833364-A-G
• rs4666865
• NM_001463.4:c.*1485T>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.*1485T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,056 control chromosomes in the GnomAD database, including 9,215 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 0.32 (9214 hom., cov: 32)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: FRZB NM_001463.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.978
• Publications: 13 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRZB	NM_001463.4	c.*1485T>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000295113.5	NP_001454.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRZB	ENST00000295113.5	c.*1485T>C		3_prime_UTR_variant	Exon 6 of 6	1	NM_001463.4	ENSP00000295113.4

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48761 AN: 151936 Hom.: 9214 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.348

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.321 AC: 48771 AN: 152054 Hom.: 9214 Cov.: 32 AF XY: 0.320 AC XY: 23748 AN XY: 74326

African (AFR) AF: 0.127 AC: 5282 AN: 41502

American (AMR) AF: 0.454 AC: 6921 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1436 AN: 3470

East Asian (EAS) AF: 0.155 AC: 799 AN: 5158

South Asian (SAS) AF: 0.397 AC: 1911 AN: 4812

European-Finnish (FIN) AF: 0.334 AC: 3530 AN: 10580

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27678 AN: 67964

Other (OTH) AF: 0.343 AC: 723 AN: 2110

Alfa AF: 0.391 Hom.: 6753

Bravo AF: 0.318

Asia WGS AF: 0.256 AC: 889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.5
DANN	Benign	0.33
PhyloP100		0.98
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: rs4666865; hg19: chr2-183698091;