Genetic Variant FZD1:c.-224T>G (chr7-91264657-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003505.2(FZD1):c.-224T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 389,516 control chromosomes in the GnomAD database, including 72,597 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 0.64 ( 31457 hom., cov: 32)

Exomes 𝑓: 0.59 ( 41140 hom. )

Consequence

FZD1
NM_003505.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.745

Publications

11 publications found

Variant links:

Genes affected

FZD1 (HGNC:4038): (frizzled class receptor 1) Members of the 'frizzled' gene family encode 7-transmembrane domain proteins that are receptors for Wnt signaling proteins. The FZD1 protein contains a signal peptide, a cysteine-rich domain in the N-terminal extracellular region, 7 transmembrane domains, and a C-terminal PDZ domain-binding motif. The FZD1 transcript is expressed in various tissues. [provided by RefSeq, Jul 2008]

FZD1 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003505.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FZD1	NM_003505.2	MANE Select	c.-224T>G		5_prime_UTR	Exon 1 of 1	NP_003496.1	Q9UP38

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FZD1	ENST00000287934.4	TSL:6 MANE Select	c.-224T>G		5_prime_UTR	Exon 1 of 1	ENSP00000287934.2	Q9UP38

Frequencies

GnomAD3 genomes

AF:

0.637

AC:

96508

AN:

151622

Hom.:

31430

Cov.:

show subpopulations

Gnomad AFR

AF:

0.781

Gnomad AMI

AF:

0.596

Gnomad AMR

AF:

0.575

Gnomad ASJ

AF:

0.554

Gnomad EAS

AF:

0.524

Gnomad SAS

AF:

0.501

Gnomad FIN

AF:

0.623

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.589

Gnomad OTH

AF:

0.611

GnomAD4 exome

AF:

0.587

AC:

139624

AN:

237786

Hom.:

41140

Cov.:

AF XY:

0.585

AC XY:

70809

AN XY:

120986

show subpopulations

African (AFR)

AF:

0.765

AC:

5133

AN:

6714

American (AMR)

AF:

0.613

AC:

4322

AN:

7056

Ashkenazi Jewish (ASJ)

AF:

0.556

AC:

4828

AN:

8688

East Asian (EAS)

AF:

0.525

AC:

11506

AN:

21922

South Asian (SAS)

AF:

0.494

AC:

1101

AN:

2230

European-Finnish (FIN)

AF:

0.625

AC:

12973

AN:

20742

Middle Eastern (MID)

AF:

0.508

AC:

622

AN:

1224

European-Non Finnish (NFE)

AF:

0.586

AC:

90048

AN:

153588

Other (OTH)

AF:

0.582

AC:

9091

AN:

15622

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

2911

5822

8734

11645

14556

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

390

780

1170

1560

1950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.637

AC:

96583

AN:

151730

Hom.:

31457

Cov.:

AF XY:

0.634

AC XY:

46991

AN XY:

74128

show subpopulations

African (AFR)

AF:

0.781

AC:

32342

AN:

41414

American (AMR)

AF:

0.575

AC:

8771

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.554

AC:

1921

AN:

3468

East Asian (EAS)

AF:

0.524

AC:

2673

AN:

5104

South Asian (SAS)

AF:

0.501

AC:

2415

AN:

4824

European-Finnish (FIN)

AF:

0.623

AC:

6560

AN:

10522

Middle Eastern (MID)

AF:

0.534

AC:

156

AN:

292

European-Non Finnish (NFE)

AF:

0.589

AC:

39921

AN:

67828

Other (OTH)

AF:

0.608

AC:

1282

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1787

3574

5362

7149

8936

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

774

1548

2322

3096

3870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.484

Hom.:

1295

Bravo

AF:

0.642

Asia WGS

AF:

0.519

AC:

1788

AN:

3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

0.74

PromoterAI

0.049

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over