rs145300245
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_003611.3(OFD1):c.1923G>A(p.Glu641Glu) variant causes a synonymous change. The variant allele was found at a frequency of 0.00455 in 1,207,779 control chromosomes in the GnomAD database, including 9 homozygotes. There are 1,687 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0029 ( 1 hom., 80 hem., cov: 23)
Exomes 𝑓: 0.0047 ( 8 hom. 1607 hem. )
Consequence
OFD1
NM_003611.3 synonymous
NM_003611.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.95
Genes affected
OFD1 (HGNC:2567): (OFD1 centriole and centriolar satellite protein) This gene is located on the X chromosome and encodes a centrosomal protein. A knockout mouse model has been used to study the effect of mutations in this gene. The mouse gene is also located on the X chromosome, however, unlike the human gene it is not subject to X inactivation. Mutations in this gene are associated with oral-facial-digital syndrome type I and Simpson-Golabi-Behmel syndrome type 2. Many pseudogenes have been identified; a single pseudogene is found on chromosome 5 while as many as fifteen have been found on the Y chromosome. [provided by RefSeq, Aug 2016]
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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=-0.47).
BP6
Variant X-13760383-G-A is Benign according to our data. Variant chrX-13760383-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 41088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-13760383-G-A is described in Lovd as [Benign]. Variant chrX-13760383-G-A is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00291 (326/111975) while in subpopulation NFE AF= 0.00504 (268/53191). AF 95% confidence interval is 0.00454. There are 1 homozygotes in gnomad4. There are 80 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
High Hemizygotes in GnomAd4 at 80 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OFD1 | NM_003611.3 | c.1923G>A | p.Glu641Glu | synonymous_variant | 16/23 | ENST00000340096.11 | NP_003602.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OFD1 | ENST00000340096.11 | c.1923G>A | p.Glu641Glu | synonymous_variant | 16/23 | 1 | NM_003611.3 | ENSP00000344314.6 |
Frequencies
GnomAD3 genomes AF: 0.00291 AC: 326AN: 111924Hom.: 1 Cov.: 23 AF XY: 0.00235 AC XY: 80AN XY: 34082
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GnomAD3 exomes AF: 0.00282 AC: 513AN: 182056Hom.: 2 AF XY: 0.00281 AC XY: 187AN XY: 66622
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GnomAD4 exome AF: 0.00472 AC: 5169AN: 1095804Hom.: 8 Cov.: 32 AF XY: 0.00445 AC XY: 1607AN XY: 361528
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GnomAD4 genome AF: 0.00291 AC: 326AN: 111975Hom.: 1 Cov.: 23 AF XY: 0.00234 AC XY: 80AN XY: 34143
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:12
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 18, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 21, 2013 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Oct 02, 2019 | - - |
not provided Benign:4
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 20, 2018 | This variant is associated with the following publications: (PMID: 18546297) - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Primary ciliary dyskinesia Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 07, 2017 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Familial aplasia of the vermis;C1510460:Orofaciodigital syndrome I Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
Retinitis pigmentosa 23;C1510460:Orofaciodigital syndrome I;C1846175:Simpson-Golabi-Behmel syndrome type 2;C2749019:Joubert syndrome 10 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 30, 2021 | - - |
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