rs776746
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 4P and 8B. PVS1_StrongBA1
The NM_001291829.2(CYP3A5):c.-253-1A>G variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.882 in 1,304,936 control chromosomes in the GnomAD database, including 522,108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association,drug response,risk factor (no stars).
Frequency
Consequence
NM_001291829.2 splice_acceptor, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.729 AC: 110783AN: 151968Hom.: 45993 Cov.: 31
GnomAD4 exome AF: 0.902 AC: 1039634AN: 1152850Hom.: 476110 Cov.: 25 AF XY: 0.901 AC XY: 496393AN XY: 551124
GnomAD4 genome AF: 0.729 AC: 110806AN: 152086Hom.: 45998 Cov.: 31 AF XY: 0.730 AC XY: 54257AN XY: 74364
ClinVar
Submissions by phenotype
Tacrolimus response Other:2
The risk of immunological complications is generally highest during the early period after kidney transplantation. Adequate immunosuppression is crucial during this critical period since lower tacrolimus exposure at approximately one week post-kidney transplantation has been associated with subsequently higher rates of acute rejection [Undre 1999, Borobia 2009, O’Seaghdha 2009, Richards 2014]. The very low dosage of 60 mg/day diltiazem affects tacrolimus exposure in CYP3A5 expressers and may reduce tacrolimus dosage requirement in CYP3A5 expressers to achieve the same exposure of the drug in nonexpressers during the first week after kidney transplantation. -
Fluctuation of tacrolimus exposure in an individual transplant recipient has been recognized as a tool for identifying patients at risk of poor outcomes (Shuker 2016, Gonzales 2020). No evidence of impact of the CYP3A5 genetic polymorphisms on tacrolimus intra-patient variability of dose-adjusted trough concentrations during 6 to 12 months after kidney transplantation was determined. However, significant influence of the polymorphisms on tacrolimus exposure was found when comparing CYP3A5 expressers with nonexpressers at months 6, 9, and 12 after transplantation, with large effect. -
refractory myasthenia gravis Other:1
Genetic polymorphisms of CYP3A5 influence the blood trough concentration and efficacy of tacrolimus for myasthenia gravis patients. CYP3A5 rs776746 were predictive factors for refractory myasthenia gravis. -
Hypertension, salt-sensitive essential, susceptibility to Other:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at