rs192720874
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The NM_003611.3(OFD1):c.1654+14T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000266 in 998,817 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 66 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 0.0013 ( 0 hom., 44 hem., cov: 22)
Exomes 𝑓: 0.00014 ( 0 hom. 22 hem. )
Consequence
OFD1
NM_003611.3 intron
NM_003611.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.59
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 -18 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
?
Variant X-13758462-T-A is Benign according to our data. Variant chrX-13758462-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 259096.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0013 (146/111920) while in subpopulation AFR AF= 0.00445 (137/30813). AF 95% confidence interval is 0.00384. There are 0 homozygotes in gnomad4. There are 44 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
BS2
?
High Hemizygotes in GnomAd4 at 44 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OFD1 | NM_003611.3 | c.1654+14T>A | intron_variant | ENST00000340096.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OFD1 | ENST00000340096.11 | c.1654+14T>A | intron_variant | 1 | NM_003611.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00121 AC: 135AN: 111869Hom.: 0 Cov.: 22 AF XY: 0.00103 AC XY: 35AN XY: 34025
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GnomAD3 exomes AF: 0.000374 AC: 66AN: 176534Hom.: 0 AF XY: 0.000209 AC XY: 13AN XY: 62106
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GnomAD4 exome AF: 0.000135 AC: 120AN: 886897Hom.: 0 Cov.: 16 AF XY: 0.0000947 AC XY: 22AN XY: 232367
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GnomAD4 genome ? AF: 0.00130 AC: 146AN: 111920Hom.: 0 Cov.: 22 AF XY: 0.00129 AC XY: 44AN XY: 34086
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 01, 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. - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Familial aplasia of the vermis;C1510460:Orofaciodigital syndrome I Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 30, 2023 | - - |
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 12, 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