chrX-68212097-T-G
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_002547.3(OPHN1):c.702+11A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00178 in 1,139,718 control chromosomes in the GnomAD database, including 3 homozygotes. There are 587 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0012 ( 0 hom., 33 hem., cov: 23)
Exomes 𝑓: 0.0019 ( 3 hom. 554 hem. )
Consequence
OPHN1
NM_002547.3 intron
NM_002547.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0500
Genes affected
OPHN1 (HGNC:8148): (oligophrenin 1) This gene encodes a Rho-GTPase-activating protein that promotes GTP hydrolysis of Rho subfamily members. Rho proteins are important mediators of intracellular signal transduction, which affects cell migration and cell morphogenesis. Mutations in this gene are responsible for OPHN1-related X-linked cognitive disability with cerebellar hypoplasia and distinctive facial dysmorhphism. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant X-68212097-T-G is Benign according to our data. Variant chrX-68212097-T-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 159478.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1, Likely_benign=1}. Variant chrX-68212097-T-G is described in Lovd as [Likely_benign].
BS2
High Hemizygotes in GnomAd4 at 33 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OPHN1 | NM_002547.3 | c.702+11A>C | intron_variant | ENST00000355520.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OPHN1 | ENST00000355520.6 | c.702+11A>C | intron_variant | 1 | NM_002547.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00117 AC: 131AN: 111938Hom.: 0 Cov.: 23 AF XY: 0.000967 AC XY: 33AN XY: 34128
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GnomAD3 exomes AF: 0.00130 AC: 213AN: 163335Hom.: 0 AF XY: 0.00112 AC XY: 58AN XY: 51569
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GnomAD4 exome AF: 0.00185 AC: 1902AN: 1027780Hom.: 3 Cov.: 20 AF XY: 0.00179 AC XY: 554AN XY: 309376
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GnomAD4 genome AF: 0.00117 AC: 131AN: 111938Hom.: 0 Cov.: 23 AF XY: 0.000967 AC XY: 33AN XY: 34128
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
X-linked intellectual disability-cerebellar hypoplasia syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 12, 2013 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 18, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 19, 2023 | - - |
Computational scores
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BayesDel_noAF
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DANN
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Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at