rs2323019

Variant names:

• chr8-28533453-G-A
• rs2323019
• NM_017412.4:c.1404+5289G>A

Variant summary

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

The NM_017412.4(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 NM_017412.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FZD3	NM_017412.4	c.1404+5289G>A		intron_variant	Intron 5 of 7	ENST00000240093.8	NP_059108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FZD3	ENST00000240093.8	c.1404+5289G>A		intron_variant	Intron 5 of 7	1	NM_017412.4	ENSP00000240093.3
FZD3	ENST00000537916.2	c.1404+5289G>A		intron_variant	Intron 4 of 6	2		ENSP00000437489.1

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

African (AFR) AF: 0.419 AC: 17374 AN: 41480

American (AMR) AF: 0.575 AC: 8787 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2217 AN: 3470

East Asian (EAS) AF: 0.633 AC: 3280 AN: 5184

South Asian (SAS) AF: 0.637 AC: 3068 AN: 4816

European-Finnish (FIN) AF: 0.614 AC: 6475 AN: 10552

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.565 AC: 38430 AN: 67994

Other (OTH) AF: 0.554 AC: 1170 AN: 2112

Alfa AF: 0.541 Hom.: 4494

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
PhyloP100		-0.16
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: rs2323019; hg19: chr8-28390970;