5-68279516-A-T

Variant names:

• chr5-68279516-A-T
• rs16897620
• NM_181523.3:c.503-86A>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_181523.3(PIK3R1):​c.503-86A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000727 in 962,852 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000067 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000074 (0 hom.)
• Consequence: PIK3R1 NM_181523.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 5 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

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.503-86A>T		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.503-86A>T		intron	N/A	ENSP00000428056.1	P27986-1
	PIK3R1	ENST00000697461.1		c.503-86A>T		intron	N/A	ENSP00000513319.1	P27986-4
	PIK3R1	ENST00000870050.1		c.503-86A>T		intron	N/A	ENSP00000540109.1

Frequencies

GnomAD3 genomes AF: 0.00000674 AC: 1 AN: 148328 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000737 AC: 6 AN: 814524 Hom.: 0 AF XY: 0.00000722 AC XY: 3 AN XY: 415512

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 18390

American (AMR) AF: 0.00 AC: 0 AN: 23098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16864

East Asian (EAS) AF: 0.00 AC: 0 AN: 32590

South Asian (SAS) AF: 0.0000193 AC: 1 AN: 51804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41114

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3948

European-Non Finnish (NFE) AF: 0.00000679 AC: 4 AN: 589132

Other (OTH) AF: 0.0000266 AC: 1 AN: 37584

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000674 AC: 1 AN: 148328 Hom.: 0 Cov.: 30 AF XY: 0.0000139 AC XY: 1 AN XY: 72042

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 39722

American (AMR) AF: 0.00 AC: 0 AN: 14954

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5092

South Asian (SAS) AF: 0.00 AC: 0 AN: 4768

European-Finnish (FIN) AF: 0.000104 AC: 1 AN: 9596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67484

Other (OTH) AF: 0.00 AC: 0 AN: 2038

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 1314

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.44
DANN	Benign	0.41
PhyloP100		-1.4

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: rs16897620; hg19: chr5-67575344;