11-125483593-C-T

Variant names:

• chr11-125483593-C-T
• rs2849222
• NM_005103.5:c.312-1960G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005103.5(FEZ1):​c.312-1960G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 152,084 control chromosomes in the GnomAD database, including 36,846 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 0.69 (36846 hom., cov: 32)
• Consequence: FEZ1 NM_005103.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FEZ1	NM_005103.5	c.312-1960G>A		intron_variant	Intron 2 of 9	ENST00000278919.8	NP_005094.1
FEZ1	XM_005271734.3	c.312-1960G>A		intron_variant	Intron 2 of 9		XP_005271791.1
FEZ1	XM_005271735.3	c.312-1960G>A		intron_variant	Intron 2 of 9		XP_005271792.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FEZ1	ENST00000278919.8	c.312-1960G>A		intron_variant	Intron 2 of 9	1	NM_005103.5	ENSP00000278919.3
FEZ1	ENST00000648911.1	c.312-1960G>A		intron_variant	Intron 4 of 11			ENSP00000497070.1
FEZ1	ENST00000392709.8	n.554-1960G>A		intron_variant	Intron 2 of 4	2
FEZ1	ENST00000532981.1	n.455-1960G>A		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104863 AN: 151966 Hom.: 36824 Cov.: 32

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.775

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.932

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.692

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

GnomAD4 genome AF: 0.690 AC: 104921 AN: 152084 Hom.: 36846 Cov.: 32 AF XY: 0.693 AC XY: 51535 AN XY: 74348

African (AFR) AF: 0.574 AC: 23810 AN: 41468

American (AMR) AF: 0.775 AC: 11849 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2389 AN: 3470

East Asian (EAS) AF: 0.932 AC: 4813 AN: 5164

South Asian (SAS) AF: 0.860 AC: 4149 AN: 4822

European-Finnish (FIN) AF: 0.659 AC: 6963 AN: 10568

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.717 AC: 48771 AN: 67982

Other (OTH) AF: 0.695 AC: 1468 AN: 2112

Alfa AF: 0.701 Hom.: 11953

Bravo AF: 0.692

Asia WGS AF: 0.862 AC: 2999 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.8
DANN	Benign	0.63
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2849222; hg19: chr11-125353489;