chr5-68238211-C-T

Variant names:

• chr5-68238211-C-T
• rs7709243
• NM_181523.3:c.334+11202C>T

Variant summary

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

The NM_181523.3(PIK3R1):​c.334+11202C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 151,622 control chromosomes in the GnomAD database, including 25,340 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 0.57 (25340 hom., cov: 32)
• Consequence: PIK3R1 NM_181523.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.879
• Publications: 12 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3R1	NM_181523.3	MANE Select	c.334+11202C>T		intron	N/A	NP_852664.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3R1	ENST00000521381.6	TSL:1 MANE Select	c.334+11202C>T		intron	N/A	ENSP00000428056.1
	PIK3R1	ENST00000517412.2	TSL:1	n.934+11202C>T		intron	N/A
	PIK3R1	ENST00000697461.1		c.334+11202C>T		intron	N/A	ENSP00000513319.1

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86074 AN: 151504 Hom.: 25280 Cov.: 32

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.568 AC: 86189 AN: 151622 Hom.: 25340 Cov.: 32 AF XY: 0.565 AC XY: 41887 AN XY: 74084

African (AFR) AF: 0.722 AC: 29832 AN: 41308

American (AMR) AF: 0.568 AC: 8670 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1608 AN: 3464

East Asian (EAS) AF: 0.756 AC: 3881 AN: 5136

South Asian (SAS) AF: 0.501 AC: 2414 AN: 4816

European-Finnish (FIN) AF: 0.438 AC: 4606 AN: 10518

Middle Eastern (MID) AF: 0.428 AC: 125 AN: 292

European-Non Finnish (NFE) AF: 0.493 AC: 33449 AN: 67820

Other (OTH) AF: 0.529 AC: 1117 AN: 2110

Alfa AF: 0.525 Hom.: 80303

Bravo AF: 0.592

Asia WGS AF: 0.639 AC: 2222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.30
DANN	Benign	0.70
PhyloP100		-0.88
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: rs7709243; hg19: chr5-67534039; COSMIC: COSV57126761; COSMIC: COSV57126761;