Genetic Variant FEZ1:c.1020+61G>A (chr11-125454069-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 NM_005103.5(FEZ1):c.1020+61G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 1,180,098 control chromosomes in the GnomAD database, including 164,741 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 0.47 ( 17333 hom., cov: 31)

Exomes 𝑓: 0.53 ( 147408 hom. )

Consequence

FEZ1
NM_005103.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.929

Publications

17 publications found

Variant links:

Genes affected

FEZ1 (HGNC:3659): (fasciculation and elongation protein zeta 1) This gene is an ortholog of the C. elegans unc-76 gene, which is necessary for normal axonal bundling and elongation within axon bundles. Expression of this gene in C. elegans unc-76 mutants can restore to the mutants partial locomotion and axonal fasciculation, suggesting that it also functions in axonal outgrowth. The N-terminal half of the gene product is highly acidic. Alternatively spliced transcript variants encoding different isoforms of this protein have been described. [provided by RefSeq, Jul 2008]

FEZ1 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=-0.87).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005103.5. 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
	FEZ1	NM_005103.5	MANE Select	c.1020+61G>A		intron	N/A	NP_005094.1	Q99689-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FEZ1	ENST00000278919.8	TSL:1 MANE Select	c.1020+61G>A	intron	N/A	ENSP00000278919.3	Q99689-1
FEZ1	ENST00000965005.1		c.1071+61G>A	intron	N/A	ENSP00000635064.1
FEZ1	ENST00000863680.1		c.1047+61G>A	intron	N/A	ENSP00000533739.1

Frequencies

GnomAD3 genomes

AF:

0.467

AC:

70966

AN:

151846

Hom.:

17329

Cov.:

show subpopulations

Gnomad AFR

AF:

0.330

Gnomad AMI

AF:

0.345

Gnomad AMR

AF:

0.438

Gnomad ASJ

AF:

0.515

Gnomad EAS

AF:

0.624

Gnomad SAS

AF:

0.655

Gnomad FIN

AF:

0.444

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.534

Gnomad OTH

AF:

0.479

GnomAD4 exome

AF:

0.530

AC:

545402

AN:

1028134

Hom.:

147408

Cov.:

AF XY:

0.536

AC XY:

280449

AN XY:

523490

show subpopulations

African (AFR)

AF:

0.325

AC:

8029

AN:

24702

American (AMR)

AF:

0.386

AC:

13388

AN:

34674

Ashkenazi Jewish (ASJ)

AF:

0.504

AC:

10583

AN:

21004

East Asian (EAS)

AF:

0.576

AC:

20501

AN:

35606

South Asian (SAS)

AF:

0.664

AC:

44507

AN:

67068

European-Finnish (FIN)

AF:

0.449

AC:

22802

AN:

50768

Middle Eastern (MID)

AF:

0.507

AC:

2313

AN:

4562

European-Non Finnish (NFE)

AF:

0.537

AC:

399314

AN:

744064

Other (OTH)

AF:

0.525

AC:

23965

AN:

45686

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

12083

24166

36249

48332

60415

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9842

19684

29526

39368

49210

<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:

0.467

AC:

71002

AN:

151964

Hom.:

17333

Cov.:

AF XY:

0.466

AC XY:

34606

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.330

AC:

13667

AN:

41420

American (AMR)

AF:

0.439

AC:

6703

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.515

AC:

1786

AN:

3468

East Asian (EAS)

AF:

0.624

AC:

3229

AN:

5176

South Asian (SAS)

AF:

0.655

AC:

3153

AN:

4812

European-Finnish (FIN)

AF:

0.444

AC:

4679

AN:

10534

Middle Eastern (MID)

AF:

0.469

AC:

138

AN:

294

European-Non Finnish (NFE)

AF:

0.534

AC:

36317

AN:

67962

Other (OTH)

AF:

0.481

AC:

1015

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1863

3725

5588

7450

9313

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

660

1320

1980

2640

3300

<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:

0.511

Hom.:

54689

Bravo

AF:

0.459

Asia WGS

AF:

0.557

AC:

1939

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.15

(source)

DANN

Benign

0.51

PhyloP100

-0.93

Mutation Taster

=100/0

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