rs16897620

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-68279516-A-G
• chr5-68279516-A-C
• chr5-68279516-A-T

Variant summary

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

The NM_181523.3(PIK3R1):​c.503-86A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 961,532 control chromosomes in the GnomAD database, including 27,694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (3867 hom., cov: 30)
  • Exomes 𝑓: 0.23 (23827 hom.)
• Consequence: PIK3R1 NM_181523.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 5-68279516-A-G is Benign according to our data. Variant chr5-68279516-A-G is described in ClinVar as Benign. ClinVar VariationId is 1241349.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.241 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.503-86A>G		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>G		intron	N/A	ENSP00000428056.1	P27986-1
	PIK3R1	ENST00000697461.1		c.503-86A>G		intron	N/A	ENSP00000513319.1	P27986-4
	PIK3R1	ENST00000870050.1		c.503-86A>G		intron	N/A	ENSP00000540109.1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 33510 AN: 148244 Hom.: 3862 Cov.: 30

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.226

GnomAD4 exome AF: 0.230 AC: 186872 AN: 813190 Hom.: 23827 AF XY: 0.230 AC XY: 95483 AN XY: 414796

African (AFR) AF: 0.181 AC: 3324 AN: 18364

American (AMR) AF: 0.228 AC: 5257 AN: 23078

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 3789 AN: 16842

East Asian (EAS) AF: 0.144 AC: 4690 AN: 32554

South Asian (SAS) AF: 0.237 AC: 12254 AN: 51726

European-Finnish (FIN) AF: 0.247 AC: 10148 AN: 41076

Middle Eastern (MID) AF: 0.175 AC: 691 AN: 3946

European-Non Finnish (NFE) AF: 0.235 AC: 137966 AN: 588068

Other (OTH) AF: 0.233 AC: 8753 AN: 37536

GnomAD4 genome AF: 0.226 AC: 33542 AN: 148342 Hom.: 3867 Cov.: 30 AF XY: 0.227 AC XY: 16334 AN XY: 72104

African (AFR) AF: 0.193 AC: 7676 AN: 39802

American (AMR) AF: 0.247 AC: 3701 AN: 14966

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 819 AN: 3454

East Asian (EAS) AF: 0.162 AC: 823 AN: 5078

South Asian (SAS) AF: 0.251 AC: 1192 AN: 4752

European-Finnish (FIN) AF: 0.250 AC: 2396 AN: 9582

Middle Eastern (MID) AF: 0.164 AC: 48 AN: 292

European-Non Finnish (NFE) AF: 0.240 AC: 16204 AN: 67452

Other (OTH) AF: 0.231 AC: 475 AN: 2058

Alfa AF: 0.223 Hom.: 1314

Bravo AF: 0.218

Asia WGS AF: 0.265 AC: 917 AN: 3458

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.53
DANN	Benign	0.29
PhyloP100		-1.4
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: rs16897620; hg19: chr5-67575344;