dbSNP rs2286948: FUZ:c.-191G>A (chr19-49813497-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The XM_011527341.3(FUZ):c.-191G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 345,758 control chromosomes in the GnomAD database, including 20,428 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 0.29 ( 7779 hom., cov: 33)

Exomes 𝑓: 0.35 ( 12649 hom. )

Consequence

FUZ
XM_011527341.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00700

Publications

9 publications found

Variant links:

Genes affected

FUZ (HGNC:26219): (fuzzy planar cell polarity protein) This gene encodes a planar cell polarity protein that is involved in ciliogenesis and directional cell movement. Knockout studies in mice exhibit neural tube defects and defective cilia, and mutations in this gene are associated with neural tube defects in humans. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2012]

FUZ Gene-Disease associations (from GenCC):

neural tube defects, susceptibility to
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

FUZ links:

Genome browser will be placed here

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=-0.77).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000313777.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FUZ	NM_025129.5	MANE Select	c.-391G>A	upstream_gene	N/A	NP_079405.2
FUZ	NM_001352262.2		c.-391G>A	upstream_gene	N/A	NP_001339191.1
FUZ	NM_001171937.2		c.-391G>A	upstream_gene	N/A	NP_001165408.1	Q9BT04-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FUZ	ENST00000529302.1	TSL:5	c.-167+110G>A	intron	N/A	ENSP00000471793.1	M0R1D4
FUZ	ENST00000313777.9	TSL:1 MANE Select	c.-391G>A	upstream_gene	N/A	ENSP00000313309.4	Q9BT04-1
FUZ	ENST00000531017.5	TSL:1	n.-188G>A	upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.292

AC:

44394

AN:

152072

Hom.:

7769

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0884

Gnomad AMI

AF:

0.311

Gnomad AMR

AF:

0.392

Gnomad ASJ

AF:

0.277

Gnomad EAS

AF:

0.511

Gnomad SAS

AF:

0.331

Gnomad FIN

AF:

0.401

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.357

Gnomad OTH

AF:

0.310

GnomAD4 exome

AF:

0.351

AC:

67945

AN:

193568

Hom.:

12649

Cov.:

AF XY:

0.349

AC XY:

36426

AN XY:

104466

show subpopulations

African (AFR)

AF:

0.0832

AC:

465

AN:

5590

American (AMR)

AF:

0.453

AC:

4204

AN:

9288

Ashkenazi Jewish (ASJ)

AF:

0.260

AC:

1281

AN:

4934

East Asian (EAS)

AF:

0.519

AC:

4212

AN:

8122

South Asian (SAS)

AF:

0.327

AC:

11811

AN:

36166

European-Finnish (FIN)

AF:

0.401

AC:

3546

AN:

8840

Middle Eastern (MID)

AF:

0.354

AC:

247

AN:

698

European-Non Finnish (NFE)

AF:

0.352

AC:

38813

AN:

110236

Other (OTH)

AF:

0.347

AC:

3366

AN:

9694

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

2027

4054

6082

8109

10136

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

290

580

870

1160

1450

<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:

0.292

AC:

44404

AN:

152190

Hom.:

7779

Cov.:

AF XY:

0.296

AC XY:

22018

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.0881

AC:

3659

AN:

41514

American (AMR)

AF:

0.392

AC:

5995

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.277

AC:

961

AN:

3468

East Asian (EAS)

AF:

0.511

AC:

2650

AN:

5188

South Asian (SAS)

AF:

0.332

AC:

1601

AN:

4828

European-Finnish (FIN)

AF:

0.401

AC:

4239

AN:

10576

Middle Eastern (MID)

AF:

0.391

AC:

115

AN:

294

European-Non Finnish (NFE)

AF:

0.357

AC:

24250

AN:

68008

Other (OTH)

AF:

0.308

AC:

651

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1543

3087

4630

6174

7717

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

452

904

1356

1808

2260

<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:

0.344

Hom.:

15837

Bravo

AF:

0.287

Asia WGS

AF:

0.394

AC:

1370

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

6.2

(source)

DANN

Benign

0.88

PhyloP100

-0.0070

PromoterAI

-0.12

Neutral

(source)

Splicing

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