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:

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=-0.87).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FEZ1	NM_005103.5 link	c.1020+61G>A	intron_variant	Intron 7 of 9	ENST00000278919.8	NP_005094.1	Q99689-1
FEZ1	XM_005271734.3 link	c.1020+61G>A	intron_variant	Intron 7 of 9		XP_005271791.1	Q99689-1
FEZ1	XM_005271735.3 link	c.1020+61G>A	intron_variant	Intron 7 of 9		XP_005271792.1	Q99689-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FEZ1	ENST00000278919.8 link	c.1020+61G>A		intron_variant	Intron 7 of 9	1	NM_005103.5	ENSP00000278919.3		Q99689-1

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over