rs2131860

Positions:

• chr8-103316081-A-G

Variant summary

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

The NM_003506.4(FZD6):​c.178-2509A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,202 control chromosomes in the GnomAD database, including 1,855 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 0.14 (1855 hom., cov: 32)
• Consequence: FZD6 NM_003506.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

Genes affected

FZD6 (HGNC:4044): (frizzled class receptor 6) This gene represents a member of the 'frizzled' gene family, which encode 7-transmembrane domain proteins that are receptors for Wnt signaling proteins. The protein encoded by this family member contains a signal peptide, a cysteine-rich domain in the N-terminal extracellular region, and seven transmembrane domains, but unlike other family members, this protein does not contain a C-terminal PDZ domain-binding motif. This protein functions as a negative regulator of the canonical Wnt/beta-catenin signaling cascade, thereby inhibiting the processes that trigger oncogenic transformation, cell proliferation, and inhibition of apoptosis. Alternative splicing results in multiple transcript variants, some of which do not encode a protein with a predicted signal peptide.[provided by RefSeq, Aug 2011]

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 (EAS) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FZD6	NM_003506.4	c.178-2509A>G		intron_variant		ENST00000358755.5	NP_003497.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FZD6	ENST00000358755.5	c.178-2509A>G		intron_variant		1	NM_003506.4	ENSP00000351605	P1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21850 AN: 152082 Hom.: 1855 Cov.: 32

Gnomad AFR AF: 0.0702

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.144 AC: 21849 AN: 152202 Hom.: 1855 Cov.: 32 AF XY: 0.150 AC XY: 11196 AN XY: 74408

Gnomad4 AFR AF: 0.0702

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.302

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.150

Alfa AF: 0.157 Hom.: 4096

Bravo AF: 0.139

Asia WGS AF: 0.258 AC: 894 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.043
DANN	Benign	0.74

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: rs2131860; hg19: chr8-104328309;