7-122302793-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001024613.4(FEZF1):c.1069+6C>G variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 1,611,538 control chromosomes in the GnomAD database, including 359,229 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (32577 hom., cov: 31)
  • Exomes 𝑓: 0.67 (326652 hom.)
• Consequence: FEZF1 NM_001024613.4 splice_donor_region, intron
• Scores: Splicing: ADA: 0.0001133
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.76

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 7-122302793-G-C is Benign according to our data. Variant chr7-122302793-G-C is described in ClinVar as [Benign]. Clinvar id is 1231901.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FEZF1	NM_001024613.4	c.1069+6C>G		splice_donor_region_variant, intron_variant		ENST00000442488.7
FEZF1	NM_001160264.2	c.919+6C>G		splice_donor_region_variant, intron_variant
FEZF1	XM_005250337.4	c.1069+6C>G		splice_donor_region_variant, intron_variant
FEZF1	XM_011516202.3	c.919+6C>G		splice_donor_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FEZF1	ENST00000442488.7	c.1069+6C>G		splice_donor_region_variant, intron_variant		1	NM_001024613.4	P2
FEZF1	ENST00000427185.2	c.919+6C>G		splice_donor_region_variant, intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99341 AN: 151842 Hom.: 32554 Cov.: 31

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.769

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.632

GnomAD3 exomes AF: 0.648 AC: 162659 AN: 251150 Hom.: 53326 AF XY: 0.650 AC XY: 88183 AN XY: 135752

Gnomad AFR exome AF: 0.620

Gnomad AMR exome AF: 0.561

Gnomad ASJ exome AF: 0.569

Gnomad EAS exome AF: 0.585

Gnomad SAS exome AF: 0.624

Gnomad FIN exome AF: 0.769

Gnomad NFE exome AF: 0.679

Gnomad OTH exome AF: 0.639

GnomAD4 exome AF: 0.667 AC: 973956 AN: 1459578 Hom.: 326652 Cov.: 41 AF XY: 0.666 AC XY: 483599 AN XY: 726190

Gnomad4 AFR exome AF: 0.619

Gnomad4 AMR exome AF: 0.571

Gnomad4 ASJ exome AF: 0.574

Gnomad4 EAS exome AF: 0.575

Gnomad4 SAS exome AF: 0.622

Gnomad4 FIN exome AF: 0.759

Gnomad4 NFE exome AF: 0.679

Gnomad4 OTH exome AF: 0.646

GnomAD4 genome AF: 0.654 AC: 99405 AN: 151960 Hom.: 32577 Cov.: 31 AF XY: 0.655 AC XY: 48670 AN XY: 74274

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.610

Gnomad4 ASJ AF: 0.569

Gnomad4 EAS AF: 0.585

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.769

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.628

Alfa AF: 0.656 Hom.: 10466

Bravo AF: 0.641

Asia WGS AF: 0.585 AC: 2038 AN: 3478

EpiCase AF: 0.657

EpiControl AF: 0.661

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 09, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	11
Dann	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00011
dbscSNV1_RF	Benign	0.010
SpliceAI score (max)		0.070		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: rs6968786; hg19: chr7-121942847; COSMIC: COSV58658866; COSMIC: COSV58658866;