chr8-28503460-C-T

Position:

• chr8-28503460-C-T

Variant summary

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

The NM_017412.4(FZD3):​c.189+258C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 151,940 control chromosomes in the GnomAD database, including 28,421 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 0.61 (28421 hom., cov: 32)
• Consequence: FZD3 NM_017412.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.805

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FZD3	NM_017412.4	c.189+258C>T		intron_variant		ENST00000240093.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FZD3	ENST00000240093.8	c.189+258C>T		intron_variant		1	NM_017412.4	P1
FZD3	ENST00000537916.2	c.189+258C>T		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92424 AN: 151822 Hom.: 28381 Cov.: 32

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.616

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

GnomAD4 genome AF: 0.609 AC: 92527 AN: 151940 Hom.: 28421 Cov.: 32 AF XY: 0.612 AC XY: 45476 AN XY: 74262

Gnomad4 AFR AF: 0.655

Gnomad4 AMR AF: 0.610

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.645

Gnomad4 SAS AF: 0.642

Gnomad4 FIN AF: 0.616

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.620

Alfa AF: 0.588 Hom.: 3634

Bravo AF: 0.609

Asia WGS AF: 0.665 AC: 2304 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.57
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: rs960914; hg19: chr8-28360977;