Variant 8-103318794-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_003506.4(FZD6):c.374+8A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000835 in 1,510,682 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0029 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00061 ( 5 hom. )

Consequence

FZD6
NM_003506.4 splice_region, intron

Scores

Splicing: ADA: 0.00006062

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0720

Variant links:

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]

FZD6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 8-103318794-A-G is Benign according to our data. Variant chr8-103318794-A-G is described in ClinVar as [Benign]. Clinvar id is 3051746.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00287 (438/152352) while in subpopulation AFR AF= 0.00936 (389/41582). AF 95% confidence interval is 0.00859. There are 3 homozygotes in gnomad4. There are 205 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FZD6	NM_003506.4 linkuse as main transcript	c.374+8A>G		splice_region_variant, intron_variant		ENST00000358755.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FZD6	ENST00000358755.5 linkuse as main transcript	c.374+8A>G		splice_region_variant, intron_variant		1	NM_003506.4	P1	O60353-1

Frequencies

GnomAD3 genomes

AF:

0.00286

AC:

436

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00933

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00538

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00122

AC:

305

AN:

250806

Hom.:

AF XY:

0.00115

AC XY:

156

AN XY:

135568

show subpopulations

Gnomad AFR exome

AF:

0.0102

Gnomad AMR exome

AF:

0.000436

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00356

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.0000706

Gnomad OTH exome

AF:

0.000983

GnomAD4 exome

AF:

0.000606

AC:

823

AN:

1358330

Hom.:

Cov.:

AF XY:

0.000688

AC XY:

469

AN XY:

682148

show subpopulations

Gnomad4 AFR exome

AF:

0.0113

Gnomad4 AMR exome

AF:

0.000561

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00374

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000747

Gnomad4 OTH exome

AF:

0.000791

GnomAD4 genome

AF:

0.00287

AC:

438

AN:

152352

Hom.:

Cov.:

AF XY:

0.00275

AC XY:

205

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00936

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00538

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00134

Hom.:

Bravo

AF:

0.00356

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

FZD6-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 27, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.9

DANN

Benign

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000061

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over