1-9715845-G-C
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong
The NM_005026.5(PIK3CD):c.371-4G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000014 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000088 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PIK3CD
NM_005026.5 splice_region, intron
NM_005026.5 splice_region, intron
Scores
2
Splicing: ADA: 0.000008829
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.27
Publications
0 publications found
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]
PIK3CD Gene-Disease associations (from GenCC):
- immunodeficiency 14Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
- immunodeficiency 14b, autosomal recessiveInheritance: AR, Unknown Classification: DEFINITIVE, MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- activated PI3K-delta syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -4 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| PIK3CD | NM_005026.5 | c.371-4G>C | splice_region_variant, intron_variant | Intron 4 of 23 | ENST00000377346.9 | NP_005017.3 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| PIK3CD | ENST00000377346.9 | c.371-4G>C | splice_region_variant, intron_variant | Intron 4 of 23 | 1 | NM_005026.5 | ENSP00000366563.4 |
Frequencies
GnomAD3 genomes 0.0000141 AC: 2AN: 141822Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
2
AN:
141822
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000877 AC: 44AN: 501820Hom.: 0 Cov.: 24 AF XY: 0.0000549 AC XY: 15AN XY: 273244 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
44
AN:
501820
Hom.:
Cov.:
24
AF XY:
AC XY:
15
AN XY:
273244
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
14910
American (AMR)
AF:
AC:
0
AN:
37100
Ashkenazi Jewish (ASJ)
AF:
AC:
1
AN:
13106
East Asian (EAS)
AF:
AC:
1
AN:
15274
South Asian (SAS)
AF:
AC:
0
AN:
69030
European-Finnish (FIN)
AF:
AC:
0
AN:
33050
Middle Eastern (MID)
AF:
AC:
0
AN:
3192
European-Non Finnish (NFE)
AF:
AC:
38
AN:
294586
Other (OTH)
AF:
AC:
3
AN:
21572
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.234
Heterozygous variant carriers
0
8
16
25
33
41
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome 0.0000141 AC: 2AN: 141928Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 68884 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
2
AN:
141928
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
68884
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
39828
American (AMR)
AF:
AC:
0
AN:
14506
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3300
East Asian (EAS)
AF:
AC:
1
AN:
4110
South Asian (SAS)
AF:
AC:
0
AN:
3902
European-Finnish (FIN)
AF:
AC:
0
AN:
8728
Middle Eastern (MID)
AF:
AC:
0
AN:
284
European-Non Finnish (NFE)
AF:
AC:
0
AN:
64398
Other (OTH)
AF:
AC:
0
AN:
2018
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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