7-122302778-G-GACA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001024613.4(FEZF1):c.1069+20_1069+21insTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.998 in 1,610,998 control chromosomes in the GnomAD database, including 802,019 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.99 (74524 hom., cov: 0)
  • Exomes 𝑓: 1.0 (727495 hom.)
• Consequence: FEZF1 NM_001024613.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.979

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 7-122302778-G-GACA is Benign according to our data. Variant chr7-122302778-G-GACA is described in ClinVar as [Benign]. Clinvar id is 1246110.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FEZF1	NM_001024613.4	c.1069+20_1069+21insTGT		intron_variant		ENST00000442488.7
FEZF1	NM_001160264.2	c.919+20_919+21insTGT		intron_variant
FEZF1	XM_005250337.4	c.1069+20_1069+21insTGT		intron_variant
FEZF1	XM_011516202.3	c.919+20_919+21insTGT		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FEZF1	ENST00000442488.7	c.1069+20_1069+21insTGT		intron_variant		1	NM_001024613.4	P2
FEZF1	ENST00000427185.2	c.919+20_919+21insTGT		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.990 AC: 150485 AN: 152078 Hom.: 74467 Cov.: 0

Gnomad AFR AF: 0.965

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.994

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.989

GnomAD3 exomes AF: 0.997 AC: 250475 AN: 251192 Hom.: 124891 AF XY: 0.998 AC XY: 135456 AN XY: 135770

Gnomad AFR exome AF: 0.964

Gnomad AMR exome AF: 0.998

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.998

GnomAD4 exome AF: 0.999 AC: 1456868 AN: 1458802 Hom.: 727495 Cov.: 37 AF XY: 0.999 AC XY: 725046 AN XY: 725910

Gnomad4 AFR exome AF: 0.963

Gnomad4 AMR exome AF: 0.998

Gnomad4 ASJ exome AF: 0.999

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.997

GnomAD4 genome AF: 0.990 AC: 150601 AN: 152196 Hom.: 74524 Cov.: 0 AF XY: 0.990 AC XY: 73627 AN XY: 74392

Gnomad4 AFR AF: 0.965

Gnomad4 AMR AF: 0.994

Gnomad4 ASJ AF: 0.999

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.990

Alfa AF: 0.995 Hom.: 13646

Bravo AF: 0.988

Asia WGS AF: 0.996 AC: 3464 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10685687; hg19: chr7-121942832;