rs409238

Positions:

• chr2-182852373-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.526+6413C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 151,978 control chromosomes in the GnomAD database, including 33,400 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 0.66 (33400 hom., cov: 31)
• Consequence: FRZB NM_001463.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.362

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]

LOC124907916 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRZB	NM_001463.4	c.526+6413C>T		intron_variant		ENST00000295113.5	NP_001454.2
LOC124907916	XR_007087330.1	n.3273+1758C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRZB	ENST00000295113.5	c.526+6413C>T		intron_variant		1	NM_001463.4	ENSP00000295113	P1

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99922 AN: 151860 Hom.: 33378 Cov.: 31

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.710

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.659

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.661

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

GnomAD4 genome AF: 0.658 AC: 99991 AN: 151978 Hom.: 33400 Cov.: 31 AF XY: 0.647 AC XY: 48057 AN XY: 74252

Gnomad4 AFR AF: 0.703

Gnomad4 AMR AF: 0.639

Gnomad4 ASJ AF: 0.732

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.656

Alfa AF: 0.665 Hom.: 5448

Bravo AF: 0.669

Asia WGS AF: 0.393 AC: 1373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.3
DANN	Benign	0.33

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: rs409238; hg19: chr2-183717101;