8-28515831-G-T

Variant names:

• chr8-28515831-G-T
• rs2874941
• NM_017412.4:c.190-4807G>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.190-4807G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 152,030 control chromosomes in the GnomAD database, including 21,766 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 (21766 hom., cov: 32)
• Consequence: FZD3 NM_017412.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.629
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.616 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.190-4807G>T		intron	N/A	NP_059108.1
	FZD3	NM_001412905.1		c.190-3294G>T		intron	N/A	NP_001399834.1
	FZD3	NM_001412917.1		c.190-3294G>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.190-4807G>T		intron	N/A	ENSP00000240093.3
	FZD3	ENST00000927846.1		c.190-3294G>T		intron	N/A	ENSP00000597905.1
	FZD3	ENST00000537916.2	TSL:2	c.190-4807G>T		intron	N/A	ENSP00000437489.1

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79866 AN: 151912 Hom.: 21757 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.526 AC: 79909 AN: 152030 Hom.: 21766 Cov.: 32 AF XY: 0.532 AC XY: 39536 AN XY: 74302

African (AFR) AF: 0.381 AC: 15813 AN: 41478

American (AMR) AF: 0.572 AC: 8744 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2217 AN: 3472

East Asian (EAS) AF: 0.631 AC: 3262 AN: 5168

South Asian (SAS) AF: 0.635 AC: 3060 AN: 4822

European-Finnish (FIN) AF: 0.614 AC: 6477 AN: 10552

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.565 AC: 38378 AN: 67946

Other (OTH) AF: 0.547 AC: 1150 AN: 2104

Alfa AF: 0.540 Hom.: 4168

Bravo AF: 0.515

Asia WGS AF: 0.630 AC: 2192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.65
DANN	Benign	0.34
PhyloP100		-0.63
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: rs2874941; hg19: chr8-28373348;