rs76096253
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The ENST00000397195.10(PAFAH1B1):c.693A>T(p.Thr231=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00245 in 1,612,858 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.013 ( 43 hom., cov: 33)
Exomes 𝑓: 0.0013 ( 44 hom. )
Consequence
PAFAH1B1
ENST00000397195.10 synonymous
ENST00000397195.10 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.884
Genes affected
PAFAH1B1 (HGNC:8574): (platelet activating factor acetylhydrolase 1b regulatory subunit 1) This locus was identified as encoding a gene that when mutated or lost caused the lissencephaly associated with Miller-Dieker lissencephaly syndrome. This gene encodes the non-catalytic alpha subunit of the intracellular Ib isoform of platelet-activating factor acteylhydrolase, a heterotrimeric enzyme that specifically catalyzes the removal of the acetyl group at the SN-2 position of platelet-activating factor (identified as 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine). Two other isoforms of intracellular platelet-activating factor acetylhydrolase exist: one composed of multiple subunits, the other, a single subunit. In addition, a single-subunit isoform of this enzyme is found in serum. [provided by RefSeq, Apr 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
Variant 17-2674081-A-T is Benign according to our data. Variant chr17-2674081-A-T is described in ClinVar as [Benign]. Clinvar id is 159541.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-2674081-A-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.884 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0134 (2036/152332) while in subpopulation AFR AF= 0.0468 (1945/41568). AF 95% confidence interval is 0.0451. There are 43 homozygotes in gnomad4. There are 1002 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 2036 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PAFAH1B1 | NM_000430.4 | c.693A>T | p.Thr231= | synonymous_variant | 8/11 | ENST00000397195.10 | NP_000421.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PAFAH1B1 | ENST00000397195.10 | c.693A>T | p.Thr231= | synonymous_variant | 8/11 | 1 | NM_000430.4 | ENSP00000380378 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0133 AC: 2029AN: 152214Hom.: 43 Cov.: 33
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GnomAD3 exomes AF: 0.00345 AC: 868AN: 251466Hom.: 21 AF XY: 0.00251 AC XY: 341AN XY: 135914
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GnomAD4 exome AF: 0.00131 AC: 1920AN: 1460526Hom.: 44 Cov.: 30 AF XY: 0.00112 AC XY: 811AN XY: 726646
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GnomAD4 genome AF: 0.0134 AC: 2036AN: 152332Hom.: 43 Cov.: 33 AF XY: 0.0135 AC XY: 1002AN XY: 74486
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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