dbSNP rs6677649: PIK3CD:c.-137-5277A>G (chr1-9686190-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005026.5(PIK3CD):c.-137-5277A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 151,964 control chromosomes in the GnomAD database, including 1,939 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. The gene PIK3CD is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.14 ( 1939 hom., cov: 31)

Consequence

PIK3CD
NM_005026.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.355

Publications

8 publications found

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]

PIK3CD links:

PIK3CD-AS2 (HGNC:51334): (PIK3CD antisense RNA 2)

PIK3CD-AS2 links:

ENSG00000301080 (HGNC:):

ENSG00000301080 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_005026.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Specifications for PIK3CD are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005026.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PIK3CD	NM_005026.5	MANE Select	c.-137-5277A>G	intron	N/A	NP_005017.3
PIK3CD	NM_001437546.1		c.-32-24234A>G	intron	N/A	NP_001424475.1	A0A2K8FKV1
PIK3CD	NM_001439206.1		c.-137-5277A>G	intron	N/A	NP_001426135.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PIK3CD	ENST00000377346.9	TSL:1 MANE Select	c.-137-5277A>G	intron	N/A	ENSP00000366563.4	O00329-1
PIK3CD	ENST00000892288.1		c.-137-5277A>G	intron	N/A	ENSP00000562347.1
PIK3CD	ENST00000698712.1		c.-32-24234A>G	intron	N/A	ENSP00000513889.1	O00329-1

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

21653

AN:

151848

Hom.:

1924

Cov.:

show subpopulations

Gnomad AFR

AF:

0.221

Gnomad AMI

AF:

0.101

Gnomad AMR

AF:

0.208

Gnomad ASJ

AF:

0.152

Gnomad EAS

AF:

0.146

Gnomad SAS

AF:

0.251

Gnomad FIN

AF:

0.0930

Gnomad MID

AF:

0.156

Gnomad NFE

AF:

0.0803

Gnomad OTH

AF:

0.136

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.143

AC:

21710

AN:

151964

Hom.:

1939

Cov.:

AF XY:

0.146

AC XY:

10864

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.221

AC:

9171

AN:

41438

American (AMR)

AF:

0.208

AC:

3174

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.152

AC:

529

AN:

3470

East Asian (EAS)

AF:

0.146

AC:

755

AN:

5180

South Asian (SAS)

AF:

0.251

AC:

1207

AN:

4812

European-Finnish (FIN)

AF:

0.0930

AC:

981

AN:

10550

Middle Eastern (MID)

AF:

0.154

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0803

AC:

5459

AN:

67952

Other (OTH)

AF:

0.141

AC:

297

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

875

1750

2625

3500

4375

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

234

468

702

936

1170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.107

Hom.:

3980

Bravo

AF:

0.154

Asia WGS

AF:

0.210

AC:

729

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.59

(source)

DANN

Benign

0.63

PhyloP100

-0.35

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over