chr8-28505861-A-G

Variant names:

• chr8-28505861-A-G
• rs7001034
• NM_017412.4:c.189+2659A>G

Variant summary

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

The NM_017412.4(FZD3):​c.189+2659A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 152,044 control chromosomes in the GnomAD database, including 29,415 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 0.62 (29415 hom., cov: 32)
• Consequence: FZD3 NM_017412.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283
• Publications: 18 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.667 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FZD3	NM_017412.4	MANE Select	c.189+2659A>G		intron	N/A	NP_059108.1
	FZD3	NM_001412905.1		c.189+2659A>G		intron	N/A	NP_001399834.1
	FZD3	NM_001412917.1		c.189+2659A>G		intron	N/A	NP_001399846.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FZD3	ENST00000240093.8	TSL:1 MANE Select	c.189+2659A>G		intron	N/A	ENSP00000240093.3
	FZD3	ENST00000537916.2	TSL:2	c.189+2659A>G		intron	N/A	ENSP00000437489.1

Frequencies

GnomAD3 genomes AF: 0.619 AC: 94068 AN: 151926 Hom.: 29375 Cov.: 32

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.619 AC: 94171 AN: 152044 Hom.: 29415 Cov.: 32 AF XY: 0.622 AC XY: 46244 AN XY: 74316

African (AFR) AF: 0.659 AC: 27297 AN: 41440

American (AMR) AF: 0.619 AC: 9448 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 2290 AN: 3468

East Asian (EAS) AF: 0.686 AC: 3543 AN: 5164

South Asian (SAS) AF: 0.645 AC: 3108 AN: 4820

European-Finnish (FIN) AF: 0.624 AC: 6597 AN: 10570

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.584 AC: 39735 AN: 67996

Other (OTH) AF: 0.632 AC: 1333 AN: 2110

Alfa AF: 0.601 Hom.: 56332

Bravo AF: 0.620

Asia WGS AF: 0.679 AC: 2360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.65
PhyloP100		-0.28
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: rs7001034; hg19: chr8-28363378;