Variant chr7-122301727-T-TA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_001024613.4(FEZF1):c.*269_*270insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00793 in 387,744 control chromosomes in the GnomAD database, including 21 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.011 ( 19 hom., cov: 32)

Exomes 𝑓: 0.0061 ( 2 hom. )

Consequence

FEZF1
NM_001024613.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.428

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 -10 ACMG points.

BP6

Variant 7-122301727-T-TA is Benign according to our data. Variant chr7-122301727-T-TA is described in ClinVar as [Likely_benign]. Clinvar id is 1189418.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0109 (1631/150266) while in subpopulation AFR AF= 0.0284 (1161/40914). AF 95% confidence interval is 0.027. There are 19 homozygotes in gnomad4. There are 741 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
FEZF1	NM_001024613.4 linkuse as main transcript	c.269_270insT	3_prime_UTR_variant	4/4	ENST00000442488.7	NP_001019784.2
FEZF1	NM_001160264.2 linkuse as main transcript	c.269_270insT	3_prime_UTR_variant	5/5		NP_001153736.1
FEZF1	XM_005250337.4 linkuse as main transcript	c.269_270insT	3_prime_UTR_variant	5/5		XP_005250394.1
FEZF1	XM_011516202.3 linkuse as main transcript	c.269_270insT	3_prime_UTR_variant	6/6		XP_011514504.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FEZF1	ENST00000442488.7 linkuse as main transcript	c.269_270insT		3_prime_UTR_variant	4/4	1	NM_001024613.4	ENSP00000411145	P2	A0PJY2-1

Frequencies

GnomAD3 genomes

AF:

0.0108

AC:

1622

AN:

150152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0282

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00602

Gnomad ASJ

AF:

0.000290

Gnomad EAS

AF:

0.00350

Gnomad SAS

AF:

0.00232

Gnomad FIN

AF:

0.00373

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00424

Gnomad OTH

AF:

0.0117

GnomAD4 exome

AF:

0.00608

AC:

1444

AN:

237478

Hom.:

Cov.:

AF XY:

0.00594

AC XY:

711

AN XY:

119630

show subpopulations

Gnomad4 AFR exome

AF:

0.0281

Gnomad4 AMR exome

AF:

0.00495

Gnomad4 ASJ exome

AF:

0.00105

Gnomad4 EAS exome

AF:

0.0123

Gnomad4 SAS exome

AF:

0.00289

Gnomad4 FIN exome

AF:

0.00563

Gnomad4 NFE exome

AF:

0.00477

Gnomad4 OTH exome

AF:

0.00657

GnomAD4 genome

AF:

0.0109

AC:

1631

AN:

150266

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

741

AN XY:

73352

show subpopulations

Gnomad4 AFR

AF:

0.0284

Gnomad4 AMR

AF:

0.00601

Gnomad4 ASJ

AF:

0.000290

Gnomad4 EAS

AF:

0.00350

Gnomad4 SAS

AF:

0.00233

Gnomad4 FIN

AF:

0.00373

Gnomad4 NFE

AF:

0.00424

Gnomad4 OTH

AF:

0.0116

Bravo

AF:

0.0115

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 22, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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