1-9654307-G-A

Variant names:

• chr1-9654307-G-A
• rs111697224
• NM_005026.5:c.-138+2505G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_005026.5(PIK3CD):​c.-138+2505G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00319 in 1,367,746 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0047 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (23 hom.)
• Consequence: PIK3CD NM_005026.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.701
• Publications: 2 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-AS1 (HGNC:32346): (PIK3CD antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (REVEL=0.142).
• BP6: Variant 1-9654307-G-A is Benign according to our data. Variant chr1-9654307-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2638189.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.003 (3647/1215404) while in subpopulation MID AF = 0.021 (94/4474). AF 95% confidence interval is 0.0176. There are 23 homozygotes in GnomAdExome4. There are 1998 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 23 Unknown,AD,AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3CD	NM_005026.5	MANE Select	c.-138+2505G>A		intron	N/A	NP_005017.3
	PIK3CD	NM_001437546.1		c.-33+2505G>A		intron	N/A	NP_001424475.1	A0A2K8FKV1
	PIK3CD	NM_001439206.1		c.-138+2505G>A		intron	N/A	NP_001426135.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3CD	ENST00000377346.9	TSL:1 MANE Select	c.-138+2505G>A		intron	N/A	ENSP00000366563.4	O00329-1
	PIK3CD-AS1	ENST00000377320.3	TSL:1	n.280C>T		non_coding_transcript_exon	Exon 1 of 2
	PIK3CD	ENST00000892288.1		c.-138+2505G>A		intron	N/A	ENSP00000562347.1

Frequencies

GnomAD3 genomes AF: 0.00465 AC: 708 AN: 152224 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00825

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00811

Gnomad ASJ AF: 0.00835

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00662

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.00206

Gnomad OTH AF: 0.00766

GnomAD2 exomes AF: 0.00372 AC: 927 AN: 249270 AF XY: 0.00404

Gnomad AFR exome AF: 0.00775

Gnomad AMR exome AF: 0.00313

Gnomad ASJ exome AF: 0.0103

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00130

Gnomad NFE exome AF: 0.00287

Gnomad OTH exome AF: 0.00529

GnomAD4 exome AF: 0.00300 AC: 3647 AN: 1215404 Hom.: 23 Cov.: 32 AF XY: 0.00332 AC XY: 1998 AN XY: 602338

African (AFR) AF: 0.00966 AC: 254 AN: 26300

American (AMR) AF: 0.00290 AC: 108 AN: 37290

Ashkenazi Jewish (ASJ) AF: 0.00941 AC: 159 AN: 16896

East Asian (EAS) AF: 0.00 AC: 0 AN: 16806

South Asian (SAS) AF: 0.00685 AC: 570 AN: 83226

European-Finnish (FIN) AF: 0.00126 AC: 41 AN: 32578

Middle Eastern (MID) AF: 0.0210 AC: 94 AN: 4474

European-Non Finnish (NFE) AF: 0.00229 AC: 2185 AN: 953830

Other (OTH) AF: 0.00536 AC: 236 AN: 44004

GnomAD4 genome AF: 0.00470 AC: 716 AN: 152342 Hom.: 1 Cov.: 32 AF XY: 0.00450 AC XY: 335 AN XY: 74496

African (AFR) AF: 0.00844 AC: 351 AN: 41574

American (AMR) AF: 0.00810 AC: 124 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00835 AC: 29 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00663 AC: 32 AN: 4828

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10616

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.00206 AC: 140 AN: 68038

Other (OTH) AF: 0.00758 AC: 16 AN: 2112

Alfa AF: 0.00407 Hom.: 4

Bravo AF: 0.00524

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.00371

EpiControl AF: 0.00367

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	6.1
DANN	Uncertain	0.98
PhyloP100		0.70
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs111697224; hg19: chr1-9714365;