18-70005060-T-C
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_173630.4(RTTN):c.6595+138A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00209 in 520,392 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0052 ( 8 hom., cov: 32)
Exomes 𝑓: 0.00080 ( 2 hom. )
Consequence
RTTN
NM_173630.4 intron
NM_173630.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.152
Genes affected
RTTN (HGNC:18654): (rotatin) This gene encodes a large protein whose specific function is unknown. Absence of the orthologous protein in mouse results in embryonic lethality with deficient axial rotation, abnormal differentiation of the neural tube, and randomized looping of the heart tube during development. In human, mutations in this gene are associated with polymicrogyria with seizures. In human fibroblasts this protein localizes at the ciliary basal bodies. Given the intracellular localization of this protein and the phenotypic effects of mutations, this gene is suspected of playing a role in the maintenance of normal ciliary structure which in turn effects the developmental process of left-right organ specification, axial rotation, and perhaps notochord development. [provided by RefSeq, Jan 2013]
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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=-0.84).
BP6
Variant 18-70005060-T-C is Benign according to our data. Variant chr18-70005060-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1206839.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0052 (792/152354) while in subpopulation AFR AF= 0.0179 (745/41582). AF 95% confidence interval is 0.0169. There are 8 homozygotes in gnomad4. There are 372 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 8 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RTTN | NM_173630.4 | c.6595+138A>G | intron_variant | ENST00000640769.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RTTN | ENST00000640769.2 | c.6595+138A>G | intron_variant | 2 | NM_173630.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00521 AC: 793AN: 152236Hom.: 8 Cov.: 32
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GnomAD4 exome AF: 0.000804 AC: 296AN: 368038Hom.: 2 AF XY: 0.000695 AC XY: 133AN XY: 191330
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GnomAD4 genome AF: 0.00520 AC: 792AN: 152354Hom.: 8 Cov.: 32 AF XY: 0.00499 AC XY: 372AN XY: 74510
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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 | Aug 17, 2018 | - - |
Computational scores
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DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at