rs2302974

Variant names:

• chr5-68273563-A-C
• rs2302974
• ENST00000517412.2:n.1108A>C

Your query was ambiguous. Multiple possible variants found:

• chr5-68273563-A-C
• chr5-68273563-A-G
• chr5-68273563-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000517412.2(PIK3R1):​n.1108A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,185,912 control chromosomes in the GnomAD database, including 24,471 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3288 hom., cov: 31)
  • Exomes 𝑓: 0.20 (21183 hom.)
• Consequence: PIK3R1 ENST00000517412.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.69
• Publications: 4 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• SHORT syndrome

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

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 5-68273563-A-C is Benign according to our data. Variant chr5-68273563-A-C is described in ClinVar as Benign. ClinVar VariationId is 1277601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3R1	NM_181523.3	c.427+81A>C		intron_variant	Intron 3 of 15	ENST00000521381.6	NP_852664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3R1	ENST00000521381.6	c.427+81A>C		intron_variant	Intron 3 of 15	1	NM_181523.3	ENSP00000428056.1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31077 AN: 151796 Hom.: 3279 Cov.: 31

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.200

GnomAD4 exome AF: 0.199 AC: 206193 AN: 1033998 Hom.: 21183 Cov.: 14 AF XY: 0.200 AC XY: 106558 AN XY: 532608

African (AFR) AF: 0.223 AC: 5544 AN: 24886

American (AMR) AF: 0.107 AC: 4676 AN: 43566

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 4961 AN: 23330

East Asian (EAS) AF: 0.179 AC: 6729 AN: 37696

South Asian (SAS) AF: 0.215 AC: 16599 AN: 77280

European-Finnish (FIN) AF: 0.227 AC: 11825 AN: 52020

Middle Eastern (MID) AF: 0.171 AC: 845 AN: 4944

European-Non Finnish (NFE) AF: 0.201 AC: 145346 AN: 723850

Other (OTH) AF: 0.208 AC: 9668 AN: 46426

GnomAD4 genome AF: 0.205 AC: 31119 AN: 151914 Hom.: 3288 Cov.: 31 AF XY: 0.206 AC XY: 15282 AN XY: 74250

African (AFR) AF: 0.224 AC: 9263 AN: 41410

American (AMR) AF: 0.153 AC: 2339 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 767 AN: 3468

East Asian (EAS) AF: 0.176 AC: 911 AN: 5172

South Asian (SAS) AF: 0.222 AC: 1066 AN: 4800

European-Finnish (FIN) AF: 0.230 AC: 2421 AN: 10548

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13689 AN: 67940

Other (OTH) AF: 0.204 AC: 430 AN: 2108

Alfa AF: 0.122 Hom.: 211

Bravo AF: 0.198

Asia WGS AF: 0.258 AC: 896 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 07, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 25% of patients studied by a panel of primary immunodeficiencies. Number of patients: 24. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.029
DANN	Benign	0.62
PhyloP100		-1.7
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: rs2302974; hg19: chr5-67569391; COSMIC: COSV57124070;