8-25422988-T-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_001083111.2(GNRH1):c.141+202A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00872 in 152,306 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0087 ( 22 hom., cov: 32)
Consequence
GNRH1
NM_001083111.2 intron
NM_001083111.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.775
Genes affected
GNRH1 (HGNC:4419): (gonadotropin releasing hormone 1) This gene encodes a preproprotein that is proteolytically processed to generate a peptide that is a member of the gonadotropin-releasing hormone (GnRH) family of peptides. Alternative splicing results in multiple transcript variants, at least one of which is secreted and then cleaved to generate gonadoliberin-1 and GnRH-associated peptide 1. Gonadoliberin-1 stimulates the release of luteinizing and follicle stimulating hormones, which are important for reproduction. Mutations in this gene are associated with hypogonadotropic hypogonadism. [provided by RefSeq, Nov 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 8-25422988-T-C is Benign according to our data. Variant chr8-25422988-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1214136.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00872 (1328/152306) while in subpopulation AFR AF= 0.0299 (1241/41564). AF 95% confidence interval is 0.0285. There are 22 homozygotes in gnomad4. There are 642 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 22 AR,Digenic gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNRH1 | NM_001083111.2 | c.141+202A>G | intron_variant | ENST00000421054.7 | |||
GNRH1 | NM_000825.3 | c.153+202A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNRH1 | ENST00000421054.7 | c.141+202A>G | intron_variant | 1 | NM_001083111.2 | P1 | |||
GNRH1 | ENST00000276414.4 | c.141+202A>G | intron_variant | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00868 AC: 1321AN: 152188Hom.: 22 Cov.: 32
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.00872 AC: 1328AN: 152306Hom.: 22 Cov.: 32 AF XY: 0.00862 AC XY: 642AN XY: 74474
GnomAD4 genome
?
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 06, 2020 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at