rs559668

Positions:

• chr11-125487880-C-T

Variant summary

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

The ENST00000278919.8(FEZ1):​c.311+1587G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,114 control chromosomes in the GnomAD database, including 3,471 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 0.21 (3471 hom., cov: 32)
• Consequence: FEZ1 ENST00000278919.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FEZ1	NM_005103.5	c.311+1587G>A		intron_variant		ENST00000278919.8	NP_005094.1
FEZ1	XM_005271734.3	c.311+1587G>A		intron_variant			XP_005271791.1
FEZ1	XM_005271735.3	c.311+1587G>A		intron_variant			XP_005271792.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FEZ1	ENST00000278919.8	c.311+1587G>A		intron_variant		1	NM_005103.5	ENSP00000278919	P1
FEZ1	ENST00000648911.1	c.311+1587G>A		intron_variant				ENSP00000497070	P1
FEZ1	ENST00000392709.8	n.553+1587G>A		intron_variant, non_coding_transcript_variant		2
FEZ1	ENST00000532981.1	n.454+1587G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31163 AN: 151996 Hom.: 3459 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.0675

Gnomad SAS AF: 0.0904

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.198

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.205 AC: 31212 AN: 152114 Hom.: 3471 Cov.: 32 AF XY: 0.202 AC XY: 15058 AN XY: 74364

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.0676

Gnomad4 SAS AF: 0.0911

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.196

Alfa AF: 0.187 Hom.: 2618

Bravo AF: 0.204

Asia WGS AF: 0.102 AC: 354 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.067
DANN	Benign	0.36

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: rs559668; hg19: chr11-125357776;