Variant 1-9715844-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The NM_005026.5(PIK3CD):c.371-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000438 in 1,611,730 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00064 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00042 ( 0 hom. )

Consequence

PIK3CD
NM_005026.5 splice_region, intron

Scores

Splicing: ADA: 0.00001660

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.817

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 (HGNC:):

PIK3CD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 1-9715844-C-T is Benign according to our data. Variant chr1-9715844-C-T is described in ClinVar as [Benign]. Clinvar id is 541089.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000643 (98/152382) while in subpopulation NFE AF= 0.00121 (82/68036). AF 95% confidence interval is 0.000994. There are 1 homozygotes in gnomad4. There are 53 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3CD	NM_005026.5 linkuse as main transcript	c.371-5C>T		splice_region_variant, intron_variant		ENST00000377346.9	NP_005017.3	O00329-1A0A2K8FKV1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3CD	ENST00000377346.9 linkuse as main transcript	c.371-5C>T		splice_region_variant, intron_variant		1	NM_005026.5	ENSP00000366563.4		O00329-1

Frequencies

GnomAD3 genomes

AF:

0.000644

AC:

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00121

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000601

AC:

145

AN:

241160

Hom.:

AF XY:

0.000590

AC XY:

AN XY:

132172

show subpopulations

Gnomad AFR exome

AF:

0.000275

Gnomad AMR exome

AF:

0.000117

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000751

Gnomad NFE exome

AF:

0.00112

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

AF:

0.000417

AC:

608

AN:

1459348

Hom.:

Cov.:

AF XY:

0.000435

AC XY:

316

AN XY:

725966

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000896

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000807

Gnomad4 NFE exome

AF:

0.000477

Gnomad4 OTH exome

AF:

0.000448

GnomAD4 genome

AF:

0.000643

AC:

AN:

152382

Hom.:

Cov.:

AF XY:

0.000711

AC XY:

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000376

Gnomad4 NFE

AF:

0.00121

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00104

Hom.:

Bravo

AF:

0.000344

EpiCase

AF:

0.000273

EpiControl

AF:

0.000535

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Immunodeficiency 14

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.4

DANN

Benign

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000017

dbscSNV1_RF

Benign

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over