ENST00000418046.1:c.-75+921A>G

Variant names:

• chr7-122309264-T-C
• rs1443753
• ENST00000418046.1:c.-75+921A>G

Variant summary

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

The ENST00000418046.1(FEZF1):​c.-75+921A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 152,112 control chromosomes in the GnomAD database, including 24,858 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 0.56 (24858 hom., cov: 33)
• Consequence: FEZF1 ENST00000418046.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.100
• Publications: 8 publications found

Genes affected

FEZF1 (HGNC:22788): (FEZ family zinc finger 1) This gene encodes a transcriptional repressor that belongs to the zinc finger double domain protein family. The encoded protein is thought to play a role in the embryonic migration of gonadotropin-releasing hormone neurons into the brain. Mutations in this gene are associated with hypogonadotropic hypogonadism-22 with anosmia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

FEZF1-AS1 (HGNC:41001): (FEZF1 antisense RNA 1)

ENSG00000293696 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000418046.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FEZF1-AS1	NR_036484.1		n.2160-320T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FEZF1	ENST00000418046.1	TSL:2	c.-75+921A>G		intron	N/A	ENSP00000406919.1
	FEZF1-AS1	ENST00000428449.5	TSL:2	n.2160-320T>C		intron	N/A
	FEZF1-AS1	ENST00000653165.1		n.351-320T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85314 AN: 151994 Hom.: 24847 Cov.: 33

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.756

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.561 AC: 85359 AN: 152112 Hom.: 24858 Cov.: 33 AF XY: 0.564 AC XY: 41935 AN XY: 74354

African (AFR) AF: 0.400 AC: 16602 AN: 41468

American (AMR) AF: 0.550 AC: 8404 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1833 AN: 3470

East Asian (EAS) AF: 0.544 AC: 2814 AN: 5170

South Asian (SAS) AF: 0.524 AC: 2525 AN: 4816

European-Finnish (FIN) AF: 0.756 AC: 8004 AN: 10592

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.635 AC: 43200 AN: 67998

Other (OTH) AF: 0.544 AC: 1148 AN: 2112

Alfa AF: 0.599 Hom.: 38768

Bravo AF: 0.541

Asia WGS AF: 0.487 AC: 1696 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.81
DANN	Benign	0.44
PhyloP100		-0.10

Splicing

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

Other links and lift over

dbSNP: rs1443753; hg19: chr7-121949318;