Variant chr7-122304153-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001024613.4(FEZF1):c.285G>C(p.Pro95=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,602,078 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 4 hom. )

Consequence

FEZF1
NM_001024613.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.02

Variant links:

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 links:

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

FEZF1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 7-122304153-C-G is Benign according to our data. Variant chr7-122304153-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 774664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.02 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FEZF1	NM_001024613.4 linkuse as main transcript	c.285G>C	p.Pro95=	synonymous_variant	1/4	ENST00000442488.7	NP_001019784.2
FEZF1-AS1	NR_036484.1 linkuse as main transcript	n.496C>G		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FEZF1	ENST00000442488.7 linkuse as main transcript	c.285G>C	p.Pro95=	synonymous_variant	1/4	1	NM_001024613.4	ENSP00000411145	P2	A0PJY2-1
FEZF1	ENST00000427185.2 linkuse as main transcript	c.285G>C	p.Pro95=	synonymous_variant	1/5	1		ENSP00000392727	A2	A0PJY2-2
FEZF1-AS1	ENST00000428449.5 linkuse as main transcript	n.496C>G		non_coding_transcript_exon_variant	1/7	2

Frequencies

GnomAD3 genomes

AF:

0.00127

AC:

194

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00237

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00128

AC:

308

AN:

239844

Hom.:

AF XY:

0.00132

AC XY:

171

AN XY:

129956

show subpopulations

Gnomad AFR exome

AF:

0.000385

Gnomad AMR exome

AF:

0.000384

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000377

Gnomad FIN exome

AF:

0.000440

Gnomad NFE exome

AF:

0.00243

Gnomad OTH exome

AF:

0.00120

GnomAD4 exome

AF:

0.00197

AC:

2855

AN:

1449760

Hom.:

Cov.:

AF XY:

0.00194

AC XY:

1394

AN XY:

719340

show subpopulations

Gnomad4 AFR exome

AF:

0.000362

Gnomad4 AMR exome

AF:

0.000500

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000235

Gnomad4 FIN exome

AF:

0.000515

Gnomad4 NFE exome

AF:

0.00242

Gnomad4 OTH exome

AF:

0.00147

GnomAD4 genome

AF:

0.00127

AC:

194

AN:

152318

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00237

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00189

Hom.:

Bravo

AF:

0.00124

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 21, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2022	FEZF1: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 20, 2023	- -

FEZF1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 30, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.8

DANN

Benign

0.77

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over