8-28557160-C-T

Variant names:

• chr8-28557160-C-T
• rs880481
• NM_017412.4:c.1787+1189C>T

Variant summary

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

The NM_017412.4(FZD3):​c.1787+1189C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 147,872 control chromosomes in the GnomAD database, including 21,548 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 0.53 (21548 hom., cov: 24)
• Consequence: FZD3 NM_017412.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.466
• Publications: 7 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]

ENSG00000290005 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017412.4. 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
	FZD3	NM_017412.4	MANE Select	c.1787+1189C>T		intron	N/A	NP_059108.1	Q9NPG1-1
	FZD3	NM_001412905.1		c.1856+1189C>T		intron	N/A	NP_001399834.1
	FZD3	NM_001412917.1		c.1856+1189C>T		intron	N/A	NP_001399846.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FZD3	ENST00000240093.8	TSL:1 MANE Select	c.1787+1189C>T		intron	N/A	ENSP00000240093.3	Q9NPG1-1
	FZD3	ENST00000927846.1		c.1856+1189C>T		intron	N/A	ENSP00000597905.1
	FZD3	ENST00000537916.2	TSL:2	c.1787+1189C>T		intron	N/A	ENSP00000437489.1	Q9NPG1-1

Frequencies

GnomAD3 genomes AF: 0.535 AC: 79055 AN: 147770 Hom.: 21542 Cov.: 24

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.594

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.553

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

GnomAD4 genome AF: 0.535 AC: 79094 AN: 147872 Hom.: 21548 Cov.: 24 AF XY: 0.540 AC XY: 38811 AN XY: 71894

African (AFR) AF: 0.422 AC: 16798 AN: 39820

American (AMR) AF: 0.578 AC: 8580 AN: 14854

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2203 AN: 3452

East Asian (EAS) AF: 0.545 AC: 2734 AN: 5018

South Asian (SAS) AF: 0.634 AC: 2962 AN: 4670

European-Finnish (FIN) AF: 0.610 AC: 5867 AN: 9616

Middle Eastern (MID) AF: 0.583 AC: 168 AN: 288

European-Non Finnish (NFE) AF: 0.566 AC: 37999 AN: 67190

Other (OTH) AF: 0.557 AC: 1146 AN: 2058

Alfa AF: 0.200 Hom.: 1243

Bravo AF: 0.523

Asia WGS AF: 0.603 AC: 2098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.6
DANN	Benign	0.49
PhyloP100		0.47
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: rs880481; hg19: chr8-28414677; COSMIC: COSV53536398;