chr5-68278091-T-C

Variant names:

• chr5-68278091-T-C
• rs17318918
• NM_181523.3:c.503-1511T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181523.3(PIK3R1):​c.503-1511T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0784 in 152,010 control chromosomes in the GnomAD database, including 594 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.

• Frequency: Genomes: 𝑓 0.078 (594 hom., cov: 31)
• Consequence: PIK3R1 NM_181523.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.349
• Publications: 6 publications found

Genes affected

PIK3R1 (HGNC:8979): (phosphoinositide-3-kinase regulatory subunit 1) Phosphatidylinositol 3-kinase phosphorylates the inositol ring of phosphatidylinositol at the 3-prime position. The enzyme comprises a 110 kD catalytic subunit and a regulatory subunit of either 85, 55, or 50 kD. This gene encodes the 85 kD regulatory subunit. Phosphatidylinositol 3-kinase plays an important role in the metabolic actions of insulin, and a mutation in this gene has been associated with insulin resistance. Alternative splicing of this gene results in four transcript variants encoding different isoforms. [provided by RefSeq, Jun 2011]

PIK3R1 Gene-Disease associations (from GenCC):

• immunodeficiency 36 with lymphoproliferation

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• PIK3R1-related immunodeficiency and SHORT syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• SHORT syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, ClinGen
• agammaglobulinemia 7, autosomal recessive

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• activated PI3K-delta syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal agammaglobulinemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181523.3. 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
	PIK3R1	NM_181523.3	MANE Select	c.503-1511T>C		intron	N/A	NP_852664.1	A0A2X0SFG1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3R1	ENST00000521381.6	TSL:1 MANE Select	c.503-1511T>C		intron	N/A	ENSP00000428056.1	P27986-1
	PIK3R1	ENST00000697461.1		c.503-1511T>C		intron	N/A	ENSP00000513319.1	P27986-4
	PIK3R1	ENST00000870050.1		c.503-1511T>C		intron	N/A	ENSP00000540109.1

Frequencies

GnomAD3 genomes AF: 0.0785 AC: 11923 AN: 151892 Hom.: 595 Cov.: 31

Gnomad AFR AF: 0.0233

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0753

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.00619

Gnomad SAS AF: 0.0534

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0782

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

GnomAD4 genome AF: 0.0784 AC: 11924 AN: 152010 Hom.: 594 Cov.: 31 AF XY: 0.0793 AC XY: 5890 AN XY: 74276

African (AFR) AF: 0.0232 AC: 962 AN: 41486

American (AMR) AF: 0.0752 AC: 1148 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 511 AN: 3470

East Asian (EAS) AF: 0.00620 AC: 32 AN: 5158

South Asian (SAS) AF: 0.0545 AC: 262 AN: 4810

European-Finnish (FIN) AF: 0.125 AC: 1314 AN: 10540

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7394 AN: 67974

Other (OTH) AF: 0.0779 AC: 164 AN: 2106

Alfa AF: 0.104 Hom.: 764

Bravo AF: 0.0719

Asia WGS AF: 0.0490 AC: 170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.44
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

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: rs17318918; hg19: chr5-67573919;