chr5-68274310-G-A

Variant names:

• chr5-68274310-G-A
• rs3730082
• ENST00000517412.2:n.1855G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000517412.2(PIK3R1):​n.1855G>A 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 0.271 in 151,918 control chromosomes in the GnomAD database, including 6,872 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.27 (6872 hom., cov: 32)
• Consequence: PIK3R1 ENST00000517412.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.283
• Publications: 9 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 5-68274310-G-A is Benign according to our data. Variant chr5-68274310-G-A is described in ClinVar as Benign. ClinVar VariationId is 1245294.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000517412.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3R1	NM_181523.3	MANE Select	c.502+297G>A		intron	N/A	NP_852664.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3R1	ENST00000517412.2	TSL:1	n.1855G>A		non_coding_transcript_exon	Exon 3 of 3
	PIK3R1	ENST00000521381.6	TSL:1 MANE Select	c.502+297G>A		intron	N/A	ENSP00000428056.1
	PIK3R1	ENST00000697461.1		c.502+297G>A		intron	N/A	ENSP00000513319.1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41154 AN: 151800 Hom.: 6863 Cov.: 32

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.271 AC: 41183 AN: 151918 Hom.: 6872 Cov.: 32 AF XY: 0.270 AC XY: 20055 AN XY: 74224

African (AFR) AF: 0.477 AC: 19752 AN: 41400

American (AMR) AF: 0.177 AC: 2705 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 684 AN: 3468

East Asian (EAS) AF: 0.231 AC: 1192 AN: 5160

South Asian (SAS) AF: 0.262 AC: 1260 AN: 4810

European-Finnish (FIN) AF: 0.204 AC: 2149 AN: 10536

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12669 AN: 67958

Other (OTH) AF: 0.251 AC: 528 AN: 2104

Alfa AF: 0.209 Hom.: 16021

Bravo AF: 0.276

Asia WGS AF: 0.247 AC: 861 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.61
PhyloP100		-0.28
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: rs3730082; hg19: chr5-67570138;