chr1-9654282-C-T

Variant names:

• chr1-9654282-C-T
• rs139847517
• NM_005026.5:c.-138+2480C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_005026.5(PIK3CD):​c.-138+2480C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00838 in 1,367,744 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0065 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0086 (58 hom.)
• Consequence: PIK3CD NM_005026.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.106
• Publications: 3 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.009).
• BP6: Variant 1-9654282-C-T is Benign according to our data. Variant chr1-9654282-C-T is described in ClinVar as Benign. ClinVar VariationId is 2638188.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 8 AD,AR,Unknown 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+2480C>T		intron	N/A	NP_005017.3
	PIK3CD	NM_001437546.1		c.-33+2480C>T		intron	N/A	NP_001424475.1	A0A2K8FKV1
	PIK3CD	NM_001439206.1		c.-138+2480C>T		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+2480C>T		intron	N/A	ENSP00000366563.4	O00329-1
	PIK3CD-AS1	ENST00000377320.3	TSL:1	n.305G>A		non_coding_transcript_exon	Exon 1 of 2
	PIK3CD	ENST00000892288.1		c.-138+2480C>T		intron	N/A	ENSP00000562347.1

Frequencies

GnomAD3 genomes AF: 0.00653 AC: 994 AN: 152232 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00171

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00995

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.000848

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00995

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00617 AC: 1539 AN: 249260 AF XY: 0.00612

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.00707

Gnomad ASJ exome AF: 0.0139

Gnomad EAS exome AF: 0.000167

Gnomad FIN exome AF: 0.00111

Gnomad NFE exome AF: 0.00871

Gnomad OTH exome AF: 0.00909

GnomAD4 exome AF: 0.00861 AC: 10470 AN: 1215394 Hom.: 58 Cov.: 32 AF XY: 0.00836 AC XY: 5034 AN XY: 602330

African (AFR) AF: 0.00144 AC: 38 AN: 26300

American (AMR) AF: 0.00762 AC: 284 AN: 37290

Ashkenazi Jewish (ASJ) AF: 0.0132 AC: 223 AN: 16896

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

South Asian (SAS) AF: 0.00219 AC: 182 AN: 83218

European-Finnish (FIN) AF: 0.00117 AC: 38 AN: 32578

Middle Eastern (MID) AF: 0.0165 AC: 74 AN: 4474

European-Non Finnish (NFE) AF: 0.00961 AC: 9168 AN: 953830

Other (OTH) AF: 0.0105 AC: 463 AN: 44002

GnomAD4 genome AF: 0.00652 AC: 993 AN: 152350 Hom.: 8 Cov.: 32 AF XY: 0.00620 AC XY: 462 AN XY: 74496

African (AFR) AF: 0.00171 AC: 71 AN: 41594

American (AMR) AF: 0.00994 AC: 152 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 45 AN: 3472

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

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4830

European-Finnish (FIN) AF: 0.000848 AC: 9 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00994 AC: 676 AN: 68036

Other (OTH) AF: 0.0109 AC: 23 AN: 2108

Alfa AF: 0.00809 Hom.: 5

Bravo AF: 0.00714

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0104

EpiControl AF: 0.0111

ClinVar

ClinVar submissions

Significance: 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	-0.91
CADD	Benign	4.6
DANN	Benign	0.75
PhyloP100		0.11
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: rs139847517; hg19: chr1-9714340; COSMIC: COSV99081017;