rs3808558

Variant names:

• chr8-103312831-G-A
• rs3808558
• NM_003506.4:c.178-5759G>A

Variant summary

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

The NM_003506.4(FZD6):​c.178-5759G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.095 in 152,178 control chromosomes in the GnomAD database, including 1,166 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 0.095 (1166 hom., cov: 32)
• Consequence: FZD6 NM_003506.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.367
• Publications: 3 publications found

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]

BAALC-AS1 (HGNC:50461): (BAALC antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003506.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FZD6	NM_003506.4	MANE Select	c.178-5759G>A		intron	N/A	NP_003497.2
	FZD6	NM_001164615.2		c.178-5759G>A		intron	N/A	NP_001158087.1
	FZD6	NM_001164616.2		c.82-5759G>A		intron	N/A	NP_001158088.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FZD6	ENST00000358755.5	TSL:1 MANE Select	c.178-5759G>A		intron	N/A	ENSP00000351605.4
	FZD6	ENST00000522566.5	TSL:1	c.178-5759G>A		intron	N/A	ENSP00000429055.1
	FZD6	ENST00000522484.5	TSL:1	n.178-5759G>A		intron	N/A	ENSP00000428301.1

Frequencies

GnomAD3 genomes AF: 0.0950 AC: 14439 AN: 152060 Hom.: 1163 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.0393

Gnomad ASJ AF: 0.0499

Gnomad EAS AF: 0.0677

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0699

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0409

Gnomad OTH AF: 0.0674

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

GnomAD4 genome AF: 0.0950 AC: 14461 AN: 152178 Hom.: 1166 Cov.: 32 AF XY: 0.0955 AC XY: 7107 AN XY: 74400

African (AFR) AF: 0.218 AC: 9063 AN: 41488

American (AMR) AF: 0.0392 AC: 600 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0499 AC: 173 AN: 3470

East Asian (EAS) AF: 0.0674 AC: 349 AN: 5176

South Asian (SAS) AF: 0.111 AC: 535 AN: 4828

European-Finnish (FIN) AF: 0.0699 AC: 741 AN: 10594

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0409 AC: 2784 AN: 68002

Other (OTH) AF: 0.0667 AC: 141 AN: 2114

Alfa AF: 0.0741 Hom.: 307

Bravo AF: 0.0986

Asia WGS AF: 0.0770 AC: 269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.2
DANN	Benign	0.71
PhyloP100		-0.37
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: rs3808558; hg19: chr8-104325059;