chr8-28498190-G-A

Position:

• chr8-28498190-G-A

Variant summary

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

The NM_017412.4(FZD3):​c.-390-1743G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 151,938 control chromosomes in the GnomAD database, including 22,064 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 (22064 hom., cov: 32)
• Consequence: FZD3 NM_017412.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560

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=-0.86).
• 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	UniProt
FZD3	NM_017412.4	c.-390-1743G>A		intron_variant		ENST00000240093.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FZD3	ENST00000240093.8	c.-390-1743G>A		intron_variant		1	NM_017412.4	P1
FZD3	ENST00000523546.1	c.-345+3847G>A		intron_variant		2
FZD3	ENST00000537916.2	c.-345+3847G>A		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80261 AN: 151820 Hom.: 22057 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.710

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.551

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

GnomAD4 genome AF: 0.529 AC: 80306 AN: 151938 Hom.: 22064 Cov.: 32 AF XY: 0.534 AC XY: 39655 AN XY: 74272

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.579

Gnomad4 SAS AF: 0.636

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.577

Gnomad4 OTH AF: 0.555

Alfa AF: 0.552 Hom.: 2938

Bravo AF: 0.518

Asia WGS AF: 0.614 AC: 2133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.57

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: rs11775139; hg19: chr8-28355707;