rs12224788

Variant names:

• chr11-125459165-C-G
• rs12224788
• NM_005103.5:c.667+1333G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-125459165-C-G
• chr11-125459165-C-T

Variant summary

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

The NM_005103.5(FEZ1):​c.667+1333G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,142 control chromosomes in the GnomAD database, including 9,220 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 0.34 (9220 hom., cov: 33)
• Consequence: FEZ1 NM_005103.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FEZ1	NM_005103.5	c.667+1333G>C		intron_variant	Intron 5 of 9	ENST00000278919.8	NP_005094.1
FEZ1	XM_005271734.3	c.667+1333G>C		intron_variant	Intron 5 of 9		XP_005271791.1
FEZ1	XM_005271735.3	c.667+1333G>C		intron_variant	Intron 5 of 9		XP_005271792.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FEZ1	ENST00000278919.8	c.667+1333G>C		intron_variant	Intron 5 of 9	1	NM_005103.5	ENSP00000278919.3

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52276 AN: 152024 Hom.: 9216 Cov.: 33

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.344 AC: 52310 AN: 152142 Hom.: 9220 Cov.: 33 AF XY: 0.341 AC XY: 25368 AN XY: 74402

African (AFR) AF: 0.281 AC: 11664 AN: 41512

American (AMR) AF: 0.319 AC: 4879 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1326 AN: 3468

East Asian (EAS) AF: 0.364 AC: 1888 AN: 5188

South Asian (SAS) AF: 0.495 AC: 2384 AN: 4818

European-Finnish (FIN) AF: 0.272 AC: 2883 AN: 10596

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.386 AC: 26211 AN: 67958

Other (OTH) AF: 0.344 AC: 726 AN: 2112

Alfa AF: 0.366 Hom.: 1264

Bravo AF: 0.342

Asia WGS AF: 0.374 AC: 1305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.7
DANN	Benign	0.39
PhyloP100		1.2
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: rs12224788; hg19: chr11-125329061;