7-122302784-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001024613.4(FEZF1):c.1069+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000177 in 1,576,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00087 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: FEZF1 NM_001024613.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.349

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-122302784-T-C is Benign according to our data. Variant chr7-122302784-T-C is described in ClinVar as [Benign]. Clinvar id is 1988604.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FEZF1	NM_001024613.4	c.1069+15A>G		intron_variant		ENST00000442488.7
FEZF1	NM_001160264.2	c.919+15A>G		intron_variant
FEZF1	XM_005250337.4	c.1069+15A>G		intron_variant
FEZF1	XM_011516202.3	c.919+15A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FEZF1	ENST00000442488.7	c.1069+15A>G		intron_variant		1	NM_001024613.4	P2
FEZF1	ENST00000427185.2	c.919+15A>G		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.000868 AC: 112 AN: 129100 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00283

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000632

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000255

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000506

Gnomad OTH AF: 0.00116

GnomAD3 exomes AF: 0.000259 AC: 65 AN: 250770 Hom.: 0 AF XY: 0.000199 AC XY: 27 AN XY: 135584

Gnomad AFR exome AF: 0.00259

Gnomad AMR exome AF: 0.000377

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000705

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000115 AC: 167 AN: 1447026 Hom.: 0 Cov.: 37 AF XY: 0.0000972 AC XY: 70 AN XY: 720490

Gnomad4 AFR exome AF: 0.00233

Gnomad4 AMR exome AF: 0.000549

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000382

Gnomad4 OTH exome AF: 0.000368

GnomAD4 genome AF: 0.000867 AC: 112 AN: 129188 Hom.: 0 Cov.: 32 AF XY: 0.000846 AC XY: 53 AN XY: 62658

Gnomad4 AFR AF: 0.00282

Gnomad4 AMR AF: 0.000631

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000255

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000506

Gnomad4 OTH AF: 0.00115

Alfa AF: 0.000427 Hom.: 0

Bravo AF: 0.000816

Asia WGS AF: 0.000577 AC: 2 AN: 3478

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

Invitae

Dec 12, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	6.7
Dann	Benign	0.36

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: rs368199722; hg19: chr7-121942838;