rs1981655
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_002014.4(FKBP4):c.394-146A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0519 in 1,318,084 control chromosomes in the GnomAD database, including 2,750 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.066 ( 450 hom., cov: 33)
Exomes 𝑓: 0.050 ( 2300 hom. )
Consequence
FKBP4
NM_002014.4 intron
NM_002014.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.00
Genes affected
FKBP4 (HGNC:3720): (FKBP prolyl isomerase 4) The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. This encoded protein is a cis-trans prolyl isomerase that binds to the immunosuppressants FK506 and rapamycin. It has high structural and functional similarity to FK506-binding protein 1A (FKBP1A), but unlike FKBP1A, this protein does not have immunosuppressant activity when complexed with FK506. It interacts with interferon regulatory factor-4 and plays an important role in immunoregulatory gene expression in B and T lymphocytes. This encoded protein is known to associate with phytanoyl-CoA alpha-hydroxylase. It can also associate with two heat shock proteins (hsp90 and hsp70) and thus may play a role in the intracellular trafficking of hetero-oligomeric forms of the steroid hormone receptors. This protein correlates strongly with adeno-associated virus type 2 vectors (AAV) resulting in a significant increase in AAV-mediated transgene expression in human cell lines. Thus this encoded protein is thought to have important implications for the optimal use of AAV vectors in human gene therapy. The human genome contains several non-transcribed pseudogenes similar to this gene. [provided by RefSeq, Sep 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FKBP4 | NM_002014.4 | c.394-146A>T | intron_variant | ENST00000001008.6 | |||
ITFG2-AS1 | NR_146317.1 | n.364-1614T>A | intron_variant, non_coding_transcript_variant | ||||
FKBP4 | XM_047428539.1 | c.259-146A>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FKBP4 | ENST00000001008.6 | c.394-146A>T | intron_variant | 1 | NM_002014.4 | P1 | |||
ENST00000547042.1 | n.151-1288T>A | intron_variant, non_coding_transcript_variant | 3 | ||||||
ITFG2-AS1 | ENST00000547834.1 | n.342-1614T>A | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0654 AC: 9946AN: 152110Hom.: 450 Cov.: 33
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GnomAD4 exome AF: 0.0501 AC: 58430AN: 1165856Hom.: 2300 AF XY: 0.0499 AC XY: 29007AN XY: 580794
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GnomAD4 genome ? AF: 0.0655 AC: 9971AN: 152228Hom.: 450 Cov.: 33 AF XY: 0.0666 AC XY: 4957AN XY: 74444
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ClinVar
Not reported inComputational 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