rs2241802

Variant names:

• chr8-28527195-A-G
• rs2241802
• NM_017412.4:c.435A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-28527195-A-G
• chr8-28527195-A-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_017412.4(FZD3):​c.435A>G​(p.Leu145Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 1,612,640 control chromosomes in the GnomAD database, including 254,266 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 (22105 hom., cov: 30)
  • Exomes 𝑓: 0.56 (232161 hom.)
• Consequence: FZD3 NM_017412.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.250
• Publications: 37 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP7: Synonymous conserved (PhyloP=0.25 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FZD3	NM_017412.4	c.435A>G	p.Leu145Leu	synonymous_variant	Exon 5 of 8	ENST00000240093.8	NP_059108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FZD3	ENST00000240093.8	c.435A>G	p.Leu145Leu	synonymous_variant	Exon 5 of 8	1	NM_017412.4	ENSP00000240093.3
FZD3	ENST00000537916.2	c.435A>G	p.Leu145Leu	synonymous_variant	Exon 4 of 7	2		ENSP00000437489.1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80903 AN: 151738 Hom.: 22095 Cov.: 30

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.549

GnomAD2 exomes AF: 0.569 AC: 142861 AN: 250878 AF XY: 0.577

Gnomad AFR exome AF: 0.409

Gnomad AMR exome AF: 0.553

Gnomad ASJ exome AF: 0.629

Gnomad EAS exome AF: 0.586

Gnomad FIN exome AF: 0.589

Gnomad NFE exome AF: 0.569

Gnomad OTH exome AF: 0.589

GnomAD4 exome AF: 0.563 AC: 821803 AN: 1460784 Hom.: 232161 Cov.: 41 AF XY: 0.566 AC XY: 411269 AN XY: 726746

African (AFR) AF: 0.422 AC: 14101 AN: 33440

American (AMR) AF: 0.555 AC: 24786 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 16326 AN: 26088

East Asian (EAS) AF: 0.561 AC: 22249 AN: 39684

South Asian (SAS) AF: 0.628 AC: 54107 AN: 86168

European-Finnish (FIN) AF: 0.589 AC: 31443 AN: 53414

Middle Eastern (MID) AF: 0.646 AC: 3720 AN: 5758

European-Non Finnish (NFE) AF: 0.559 AC: 620849 AN: 1111220

Other (OTH) AF: 0.567 AC: 34222 AN: 60360

GnomAD4 genome AF: 0.533 AC: 80952 AN: 151856 Hom.: 22105 Cov.: 30 AF XY: 0.538 AC XY: 39936 AN XY: 74204

African (AFR) AF: 0.418 AC: 17320 AN: 41404

American (AMR) AF: 0.574 AC: 8769 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2208 AN: 3468

East Asian (EAS) AF: 0.578 AC: 2968 AN: 5134

South Asian (SAS) AF: 0.635 AC: 3053 AN: 4808

European-Finnish (FIN) AF: 0.602 AC: 6351 AN: 10544

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38307 AN: 67920

Other (OTH) AF: 0.553 AC: 1163 AN: 2104

Alfa AF: 0.558 Hom.: 108851

Bravo AF: 0.525

Asia WGS AF: 0.618 AC: 2146 AN: 3476

EpiCase AF: 0.573

EpiControl AF: 0.566

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	9.9
DANN	Benign	0.80
PhyloP100		0.25
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: rs2241802; hg19: chr8-28384712; COSMIC: COSV53534310; COSMIC: COSV53534310;