Variant chr7-122302793-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000442488.7(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
ENST00000442488.7 splice_donor_region, intron

Scores

Splicing: ADA: 0.0001133

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.76

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Effect	MANE	Protein
FEZF1	NM_001024613.4 linkuse as main transcript	c.1069+6C>G	splice_donor_region_variant, intron_variant	ENST00000442488.7	NP_001019784.2
FEZF1	NM_001160264.2 linkuse as main transcript	c.919+6C>G	splice_donor_region_variant, intron_variant		NP_001153736.1
FEZF1	XM_005250337.4 linkuse as main transcript	c.1069+6C>G	splice_donor_region_variant, intron_variant		XP_005250394.1
FEZF1	XM_011516202.3 linkuse as main transcript	c.919+6C>G	splice_donor_region_variant, intron_variant		XP_011514504.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FEZF1	ENST00000442488.7 linkuse as main transcript	c.1069+6C>G		splice_donor_region_variant, intron_variant		1	NM_001024613.4	ENSP00000411145	P2	A0PJY2-1
FEZF1	ENST00000427185.2 linkuse as main transcript	c.919+6C>G		splice_donor_region_variant, intron_variant		1		ENSP00000392727	A2	A0PJY2-2

Frequencies

GnomAD3 genomes

AF:

0.654

AC:

99341

AN:

151842

Hom.:

32554

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.666

AC XY:

483599

AN XY:

726190

show subpopulations

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.:

AF XY:

0.655

AC XY:

48670

AN XY:

74274

show subpopulations

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

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

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