7-122302388-GA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001024613.4(FEZF1):c.1070-34del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0517 in 1,512,026 control chromosomes in the GnomAD database, including 4,265 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (1635 hom., cov: 31)
  • Exomes 𝑓: 0.046 (2630 hom.)
• Consequence: FEZF1 NM_001024613.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.172

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 7-122302388-GA-G is Benign according to our data. Variant chr7-122302388-GA-G is described in ClinVar as [Benign]. Clinvar id is 1243725.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FEZF1	NM_001024613.4	c.1070-34del		intron_variant		ENST00000442488.7
FEZF1	NM_001160264.2	c.920-34del		intron_variant
FEZF1	XM_005250337.4	c.1070-34del		intron_variant
FEZF1	XM_011516202.3	c.920-34del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FEZF1	ENST00000442488.7	c.1070-34del		intron_variant		1	NM_001024613.4	P2
FEZF1	ENST00000427185.2	c.920-34del		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15475 AN: 148442 Hom.: 1631 Cov.: 31

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.0584

Gnomad ASJ AF: 0.0479

Gnomad EAS AF: 0.0115

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0141

Gnomad MID AF: 0.148

Gnomad NFE AF: 0.0362

Gnomad OTH AF: 0.0927

GnomAD3 exomes AF: 0.0864 AC: 14559 AN: 168574 Hom.: 925 AF XY: 0.0853 AC XY: 7851 AN XY: 92000

Gnomad AFR exome AF: 0.338

Gnomad AMR exome AF: 0.0612

Gnomad ASJ exome AF: 0.0692

Gnomad EAS exome AF: 0.0159

Gnomad SAS exome AF: 0.156

Gnomad FIN exome AF: 0.0222

Gnomad NFE exome AF: 0.0567

Gnomad OTH exome AF: 0.0801

GnomAD4 exome AF: 0.0459 AC: 62618 AN: 1363472 Hom.: 2630 Cov.: 32 AF XY: 0.0478 AC XY: 32424 AN XY: 678934

Gnomad4 AFR exome AF: 0.297

Gnomad4 AMR exome AF: 0.0449

Gnomad4 ASJ exome AF: 0.0513

Gnomad4 EAS exome AF: 0.0204

Gnomad4 SAS exome AF: 0.113

Gnomad4 FIN exome AF: 0.0161

Gnomad4 NFE exome AF: 0.0344

Gnomad4 OTH exome AF: 0.0607

GnomAD4 genome AF: 0.104 AC: 15496 AN: 148554 Hom.: 1635 Cov.: 31 AF XY: 0.103 AC XY: 7424 AN XY: 72378

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.0584

Gnomad4 ASJ AF: 0.0479

Gnomad4 EAS AF: 0.0115

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.0141

Gnomad4 NFE AF: 0.0362

Gnomad4 OTH AF: 0.0912

Alfa AF: 0.0339 Hom.: 35

Bravo AF: 0.113

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs144032772; hg19: chr7-121942442;