7-122302620-C-A

Position:

• chr7-122302620-C-A

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.1069+179G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,076 control chromosomes in the GnomAD database, including 8,876 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.32 (8876 hom., cov: 33)
• Consequence: FEZF1 NM_001024613.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.267

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=-0.8).
• BP6: Variant 7-122302620-C-A is Benign according to our data. Variant chr7-122302620-C-A is described in ClinVar as [Benign]. Clinvar id is 1263455.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FEZF1	NM_001024613.4	c.1069+179G>T		intron_variant		ENST00000442488.7	NP_001019784.2
FEZF1	NM_001160264.2	c.919+179G>T		intron_variant			NP_001153736.1
FEZF1	XM_005250337.4	c.1069+179G>T		intron_variant			XP_005250394.1
FEZF1	XM_011516202.3	c.919+179G>T		intron_variant			XP_011514504.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FEZF1	ENST00000442488.7	c.1069+179G>T		intron_variant		1	NM_001024613.4	ENSP00000411145	P2
FEZF1	ENST00000427185.2	c.919+179G>T		intron_variant		1		ENSP00000392727	A2

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48718 AN: 151958 Hom.: 8879 Cov.: 33

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.320 AC: 48719 AN: 152076 Hom.: 8876 Cov.: 33 AF XY: 0.317 AC XY: 23532 AN XY: 74332

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.309

Alfa AF: 0.378 Hom.: 3890

Bravo AF: 0.300

Asia WGS AF: 0.112 AC: 392 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	-0.80
CADD	Benign	11
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: rs6968240; hg19: chr7-121942674; COSMIC: COSV58660052; COSMIC: COSV58660052;