rs2323019

Positions:

• chr8-28533453-G-A

Variant summary

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

The ENST00000240093.8(FZD3):​c.1404+5289G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 152,090 control chromosomes in the GnomAD database, including 22,469 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 0.54 (22469 hom., cov: 33)
• Consequence: FZD3 ENST00000240093.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158

Genes affected

FZD3 (HGNC:4041): (frizzled class receptor 3) This gene is a member of the frizzled gene family. Members of this family encode seven-transmembrane domain proteins that are receptors for the wingless type MMTV integration site family of signaling proteins. Most frizzled receptors are coupled to the beta-catenin canonical signaling pathway. The function of this protein is unknown, although it may play a role in mammalian hair follicle development. Alternative splicing results in multiple transcript variants. This gene is a susceptibility locus for schizophrenia. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FZD3	NM_017412.4	c.1404+5289G>A		intron_variant		ENST00000240093.8	NP_059108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FZD3	ENST00000240093.8	c.1404+5289G>A		intron_variant		1	NM_017412.4	ENSP00000240093	P1
FZD3	ENST00000537916.2	c.1404+5289G>A		intron_variant		2		ENSP00000437489	P1

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81566 AN: 151972 Hom.: 22459 Cov.: 33

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.537 AC: 81613 AN: 152090 Hom.: 22469 Cov.: 33 AF XY: 0.542 AC XY: 40319 AN XY: 74360

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.575

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.633

Gnomad4 SAS AF: 0.637

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.565

Gnomad4 OTH AF: 0.554

Alfa AF: 0.546 Hom.: 3781

Bravo AF: 0.528

Asia WGS AF: 0.635 AC: 2207 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.85
DANN	Benign	0.18

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: rs2323019; hg19: chr8-28390970;