7-122302567-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001024613.4(FEZF1):c.1070-212T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,868 control chromosomes in the GnomAD database, including 24,050 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.55 (24050 hom., cov: 31)
• Consequence: FEZF1 NM_001024613.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0570

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-122302567-A-G is Benign according to our data. Variant chr7-122302567-A-G is described in ClinVar as [Benign]. Clinvar id is 1269885.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FEZF1	NM_001024613.4	c.1070-212T>C		intron_variant		ENST00000442488.7
FEZF1	NM_001160264.2	c.920-212T>C		intron_variant
FEZF1	XM_005250337.4	c.1070-212T>C		intron_variant
FEZF1	XM_011516202.3	c.920-212T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FEZF1	ENST00000442488.7	c.1070-212T>C		intron_variant		1	NM_001024613.4	P2
FEZF1	ENST00000427185.2	c.920-212T>C		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82844 AN: 151750 Hom.: 24039 Cov.: 31

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.756

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.535

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.546 AC: 82885 AN: 151868 Hom.: 24050 Cov.: 31 AF XY: 0.548 AC XY: 40704 AN XY: 74228

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.548

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.567

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.756

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.532

Alfa AF: 0.621 Hom.: 36565

Bravo AF: 0.524

Asia WGS AF: 0.490 AC: 1705 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

Aug 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.3
Dann	Benign	0.45

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: rs11978249; hg19: chr7-121942621;