chr7-122302795-A-G
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001024613.4(FEZF1):c.1069+4T>C variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0323 in 1,612,876 control chromosomes in the GnomAD database, including 1,022 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.026 ( 70 hom., cov: 32)
Exomes 𝑓: 0.033 ( 952 hom. )
Consequence
FEZF1
NM_001024613.4 splice_donor_region, intron
NM_001024613.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.00001987
2
Clinical Significance
Conservation
PhyloP100: 0.433
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
Variant 7-122302795-A-G is Benign according to our data. Variant chr7-122302795-A-G is described in ClinVar as [Benign]. Clinvar id is 1267416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0257 (3899/151902) while in subpopulation NFE AF= 0.0369 (2509/67996). AF 95% confidence interval is 0.0357. There are 70 homozygotes in gnomad4. There are 1946 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 70 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FEZF1 | NM_001024613.4 | c.1069+4T>C | splice_donor_region_variant, intron_variant | ENST00000442488.7 | |||
FEZF1 | NM_001160264.2 | c.919+4T>C | splice_donor_region_variant, intron_variant | ||||
FEZF1 | XM_005250337.4 | c.1069+4T>C | splice_donor_region_variant, intron_variant | ||||
FEZF1 | XM_011516202.3 | c.919+4T>C | splice_donor_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FEZF1 | ENST00000442488.7 | c.1069+4T>C | splice_donor_region_variant, intron_variant | 1 | NM_001024613.4 | P2 | |||
FEZF1 | ENST00000427185.2 | c.919+4T>C | splice_donor_region_variant, intron_variant | 1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0257 AC: 3900AN: 151784Hom.: 70 Cov.: 32
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GnomAD3 exomes AF: 0.0269 AC: 6764AN: 251342Hom.: 126 AF XY: 0.0271 AC XY: 3680AN XY: 135848
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GnomAD4 exome AF: 0.0330 AC: 48257AN: 1460974Hom.: 952 Cov.: 35 AF XY: 0.0322 AC XY: 23428AN XY: 726864
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GnomAD4 genome ? AF: 0.0257 AC: 3899AN: 151902Hom.: 70 Cov.: 32 AF XY: 0.0262 AC XY: 1946AN XY: 74202
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 17, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at