chr8-28553555-T-C

Variant names:

• chr8-28553555-T-C
• rs10092491
• NM_017412.4:c.1553+1804T>C

Variant summary

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

The NM_017412.4(FZD3):​c.1553+1804T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 151,998 control chromosomes in the GnomAD database, including 26,238 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 0.59 (26238 hom., cov: 32)
• Consequence: FZD3 NM_017412.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211
• 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]

ENSG00000290005 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FZD3	NM_017412.4	c.1553+1804T>C		intron_variant	Intron 6 of 7	ENST00000240093.8	NP_059108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FZD3	ENST00000240093.8	c.1553+1804T>C		intron_variant	Intron 6 of 7	1	NM_017412.4	ENSP00000240093.3

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88907 AN: 151880 Hom.: 26211 Cov.: 32

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.585 AC: 88986 AN: 151998 Hom.: 26238 Cov.: 32 AF XY: 0.590 AC XY: 43813 AN XY: 74292

African (AFR) AF: 0.586 AC: 24280 AN: 41448

American (AMR) AF: 0.595 AC: 9075 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2233 AN: 3472

East Asian (EAS) AF: 0.646 AC: 3326 AN: 5148

South Asian (SAS) AF: 0.638 AC: 3078 AN: 4826

European-Finnish (FIN) AF: 0.613 AC: 6477 AN: 10560

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.566 AC: 38451 AN: 67966

Other (OTH) AF: 0.592 AC: 1250 AN: 2112

Alfa AF: 0.566 Hom.: 18850

Bravo AF: 0.584

Asia WGS AF: 0.654 AC: 2277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.6
DANN	Benign	0.41
PhyloP100		-0.21
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: rs10092491; hg19: chr8-28411072;