rs2067135

Variant names:

• chr5-68216763-A-AAACCACAGCTCTAACACTAGTGAGCTCT
• rs2067135
• NM_181523.3:c.-387+829_-387+830insACTAGTGAGCTCTAACCACAGCTCTAAC

Your query was ambiguous. Multiple possible variants found:

• chr5-68216763-A-AAACCACAGCTCTAACACTAGTGAGCTCT
• chr5-68216763-A-AAACCACAGCTCTAACATTAGTGAGCTCT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_181523.3(PIK3R1):​c.-387+829_-387+830insACTAGTGAGCTCTAACCACAGCTCTAAC variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (21821 hom., cov: 0)
• Consequence: PIK3R1 NM_181523.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20
• Publications: 1 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.711 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.-387+829_-387+830insACTAGTGAGCTCTAACCACAGCTCTAAC		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.-387+829_-387+830insACTAGTGAGCTCTAACCACAGCTCTAAC		intron	N/A	ENSP00000428056.1	P27986-1
	PIK3R1	ENST00000517412.2	TSL:1	n.214+825_214+826insACTAGTGAGCTCTAACCACAGCTCTAAC		intron	N/A
	PIK3R1	ENST00000517643.2	TSL:3	c.-1407_-1406insACTAGTGAGCTCTAACCACAGCTCTAAC		5_prime_UTR	Exon 1 of 16	ENSP00000513333.1	P27986-1

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78416 AN: 151050 Hom.: 21760 Cov.: 0

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.520 AC: 78540 AN: 151168 Hom.: 21821 Cov.: 0 AF XY: 0.517 AC XY: 38173 AN XY: 73866

African (AFR) AF: 0.718 AC: 29471 AN: 41048

American (AMR) AF: 0.495 AC: 7521 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1005 AN: 3460

East Asian (EAS) AF: 0.723 AC: 3709 AN: 5128

South Asian (SAS) AF: 0.447 AC: 2136 AN: 4774

European-Finnish (FIN) AF: 0.388 AC: 4068 AN: 10472

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.430 AC: 29119 AN: 67776

Other (OTH) AF: 0.459 AC: 962 AN: 2096

Alfa AF: 0.406 Hom.: 1381

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2067135; hg19: chr5-67512591;