1-9715845-G-T

Variant names:

• chr1-9715845-G-T
• rs775036315
• NM_005026.5:c.371-4G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_005026.5(PIK3CD):​c.371-4G>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 0.0000248 in 646,038 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000070 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: PIK3CD NM_005026.5 splice_region, intron
• Scores: Splicing: ADA: 0.00004327
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 14

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• immunodeficiency 14b, autosomal recessive

  Inheritance: AR, Unknown Classification: DEFINITIVE, MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• activated PI3K-delta syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-9715845-G-T is Benign according to our data. Variant chr1-9715845-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 941754.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3CD	NM_005026.5	c.371-4G>T		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>T		splice_region_variant, intron_variant	Intron 4 of 23	1	NM_005026.5	ENSP00000366563.4

Frequencies

GnomAD3 genomes AF: 0.00000705 AC: 1 AN: 141866 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000252

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000664 AC: 16 AN: 240858 AF XY: 0.0000454

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000467

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000298 AC: 15 AN: 504172 Hom.: 0 Cov.: 24 AF XY: 0.0000255 AC XY: 7 AN XY: 274380

African (AFR) AF: 0.00 AC: 0 AN: 14972

American (AMR) AF: 0.000377 AC: 14 AN: 37116

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13152

East Asian (EAS) AF: 0.00 AC: 0 AN: 15334

South Asian (SAS) AF: 0.00 AC: 0 AN: 69072

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33098

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3198

European-Non Finnish (NFE) AF: 0.00000337 AC: 1 AN: 296554

Other (OTH) AF: 0.00 AC: 0 AN: 21676

GnomAD4 genome AF: 0.00000705 AC: 1 AN: 141866 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 68804

African (AFR) AF: 0.0000252 AC: 1 AN: 39756

American (AMR) AF: 0.00 AC: 0 AN: 14490

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3300

East Asian (EAS) AF: 0.00 AC: 0 AN: 4120

South Asian (SAS) AF: 0.00 AC: 0 AN: 3902

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8732

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64404

Other (OTH) AF: 0.00 AC: 0 AN: 2002

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Immunodeficiency 14 Benign:1

Nov 07, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.014
DANN	Benign	0.42
PhyloP100		-1.3

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000043
dbscSNV1_RF	Benign	0.048
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs775036315; hg19: chr1-9775903;