7-122301727-T-TA

Position:

• chr7-122301727-T-TA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.428

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 -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	HGVSp	Effect	#exon/exons	MANE	UniProt
FEZF1	NM_001024613.4	c.*269_*270insT		3_prime_UTR_variant	4/4	ENST00000442488.7
FEZF1	NM_001160264.2	c.*269_*270insT		3_prime_UTR_variant	5/5
FEZF1	XM_005250337.4	c.*269_*270insT		3_prime_UTR_variant	5/5
FEZF1	XM_011516202.3	c.*269_*270insT		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FEZF1	ENST00000442488.7	c.*269_*270insT		3_prime_UTR_variant	4/4	1	NM_001024613.4	P2

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 1622 AN: 150152 Hom.: 19 Cov.: 32

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.: 2 Cov.: 3 AF XY: 0.00594 AC XY: 711 AN XY: 119630

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.: 19 Cov.: 32 AF XY: 0.0101 AC XY: 741 AN XY: 73352

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: 14 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

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: rs201400828; hg19: chr7-121941781;