rs11220082

Positions:

• chr11-125454069-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.929

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FEZ1	NM_005103.5	c.1020+61G>A		intron_variant		ENST00000278919.8	NP_005094.1
FEZ1	XM_005271734.3	c.1020+61G>A		intron_variant			XP_005271791.1
FEZ1	XM_005271735.3	c.1020+61G>A		intron_variant			XP_005271792.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FEZ1	ENST00000278919.8	c.1020+61G>A		intron_variant		1	NM_005103.5	ENSP00000278919.3

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70966 AN: 151846 Hom.: 17329 Cov.: 31

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.: 12 AF XY: 0.536 AC XY: 280449 AN XY: 523490

Gnomad4 AFR exome AF: 0.325

Gnomad4 AMR exome AF: 0.386

Gnomad4 ASJ exome AF: 0.504

Gnomad4 EAS exome AF: 0.576

Gnomad4 SAS exome AF: 0.664

Gnomad4 FIN exome AF: 0.449

Gnomad4 NFE exome AF: 0.537

Gnomad4 OTH exome AF: 0.525

GnomAD4 genome AF: 0.467 AC: 71002 AN: 151964 Hom.: 17333 Cov.: 31 AF XY: 0.466 AC XY: 34606 AN XY: 74274

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.439

Gnomad4 ASJ AF: 0.515

Gnomad4 EAS AF: 0.624

Gnomad4 SAS AF: 0.655

Gnomad4 FIN AF: 0.444

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.481

Alfa AF: 0.522 Hom.: 34982

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
DANN	Benign	0.51

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

LitVar

Other links and lift over

dbSNP: rs11220082; hg19: chr11-125323965; COSMIC: COSV54027186; COSMIC: COSV54027186;