rs145697393

Positions:

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

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -5.63
Variant links:
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]

Genome browser will be placed here

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
PIK3CDNM_005026.5 linkuse as main transcriptc.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
PIK3CDENST00000377346.9 linkuse as main transcriptc.708G>A p.Pro236= synonymous_variant 6/241 NM_005026.5 ENSP00000366563 P3O00329-1

Frequencies

GnomAD3 genomes
AF:
0.00430
AC:
654
AN:
152188
Hom.:
8
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0146
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00430
GnomAD3 exomes
AF:
0.00115
AC:
274
AN:
239114
Hom.:
0
AF XY:
0.000844
AC XY:
110
AN XY:
130352
show subpopulations
Gnomad AFR exome
AF:
0.0142
Gnomad AMR exome
AF:
0.00125
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000668
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000656
Gnomad OTH exome
AF:
0.00120
GnomAD4 exome
AF:
0.000528
AC:
768
AN:
1455708
Hom.:
4
Cov.:
33
AF XY:
0.000453
AC XY:
328
AN XY:
724096
show subpopulations
Gnomad4 AFR exome
AF:
0.0161
Gnomad4 AMR exome
AF:
0.00132
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000506
Gnomad4 SAS exome
AF:
0.000152
Gnomad4 FIN exome
AF:
0.0000191
Gnomad4 NFE exome
AF:
0.0000576
Gnomad4 OTH exome
AF:
0.00145
GnomAD4 genome
AF:
0.00430
AC:
655
AN:
152306
Hom.:
8
Cov.:
33
AF XY:
0.00431
AC XY:
321
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.0146
Gnomad4 AMR
AF:
0.00196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00425
Alfa
AF:
0.00211
Hom.:
0
Bravo
AF:
0.00532
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

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 submitterclinical testingGenetic Services Laboratory, University of ChicagoNov 09, 2021- -
not provided Benign:1
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Immunodeficiency 14 Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 29, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
1.2
DANN
Benign
0.81

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs145697393; hg19: chr1-9776605; API