rs145697393
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The ENST00000377346.9(PIK3CD):c.708G>A(p.Pro236=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000885 in 1,608,014 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0043 ( 8 hom., cov: 33)
Exomes 𝑓: 0.00053 ( 4 hom. )
Consequence
PIK3CD
ENST00000377346.9 synonymous
ENST00000377346.9 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -5.63
Genes affected
PIK3CD (HGNC:8977): (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta) Phosphoinositide 3-kinases (PI3Ks) phosphorylate inositol lipids and are involved in the immune response. The protein encoded by this gene is a class I PI3K found primarily in leukocytes. Like other class I PI3Ks (p110-alpha p110-beta, and p110-gamma), the encoded protein binds p85 adapter proteins and GTP-bound RAS. However, unlike the other class I PI3Ks, this protein phosphorylates itself, not p85 protein.[provided by RefSeq, Jul 2010]
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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=-0.8).
BP6
Variant 1-9716547-G-A is Benign according to our data. Variant chr1-9716547-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 474034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-5.63 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0043 (655/152306) while in subpopulation AFR AF= 0.0146 (607/41560). AF 95% confidence interval is 0.0136. There are 8 homozygotes in gnomad4. There are 321 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 8 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PIK3CD | NM_005026.5 | c.708G>A | p.Pro236= | synonymous_variant | 6/24 | ENST00000377346.9 | NP_005017.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PIK3CD | ENST00000377346.9 | c.708G>A | p.Pro236= | synonymous_variant | 6/24 | 1 | NM_005026.5 | ENSP00000366563 | P3 |
Frequencies
GnomAD3 genomes AF: 0.00430 AC: 654AN: 152188Hom.: 8 Cov.: 33
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GnomAD3 exomes AF: 0.00115 AC: 274AN: 239114Hom.: 0 AF XY: 0.000844 AC XY: 110AN XY: 130352
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GnomAD4 exome AF: 0.000528 AC: 768AN: 1455708Hom.: 4 Cov.: 33 AF XY: 0.000453 AC XY: 328AN XY: 724096
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GnomAD4 genome AF: 0.00430 AC: 655AN: 152306Hom.: 8 Cov.: 33 AF XY: 0.00431 AC XY: 321AN XY: 74484
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 09, 2021 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Immunodeficiency 14 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
Computational scores
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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