rs7930295

Positions:

• chr11-125443703-A-G
• chr11-125443703-A-T

Variant summary

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

The NM_005103.5(FEZ1):​c.*2392T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,164 control chromosomes in the GnomAD database, including 1,614 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 0.14 (1614 hom., cov: 32)
• Consequence: FEZ1 NM_005103.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FEZ1	NM_005103.5	c.*2392T>C		3_prime_UTR_variant	10/10	ENST00000278919.8	NP_005094.1
FEZ1	XM_005271734.3	c.*2392T>C		3_prime_UTR_variant	10/10		XP_005271791.1
FEZ1	XM_005271735.3	c.*2392T>C		3_prime_UTR_variant	10/10		XP_005271792.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FEZ1	ENST00000278919.8	c.*2392T>C		3_prime_UTR_variant	10/10	1	NM_005103.5	ENSP00000278919	P1
FEZ1	ENST00000648911.1	c.*2392T>C		3_prime_UTR_variant	12/12			ENSP00000497070	P1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21252 AN: 152046 Hom.: 1614 Cov.: 32

Gnomad AFR AF: 0.0972

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.140 AC: 21255 AN: 152164 Hom.: 1614 Cov.: 32 AF XY: 0.141 AC XY: 10524 AN XY: 74382

Gnomad4 AFR AF: 0.0969

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.142

Alfa AF: 0.137 Hom.: 257

Bravo AF: 0.136

Asia WGS AF: 0.190 AC: 660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.35

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7930295; hg19: chr11-125313599;