17-8803133-T-C

Variant names:

• chr17-8803133-T-C
• rs2242375
• NM_001010855.4:c.*140A>G

Variant summary

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

The NM_001010855.4(PIK3R6):​c.*140A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 1,117,060 control chromosomes in the GnomAD database, including 109,749 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 0.35 (11458 hom., cov: 32)
  • Exomes 𝑓: 0.45 (98291 hom.)
• Consequence: PIK3R6 NM_001010855.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.291
• Publications: 9 publications found

Genes affected

PIK3R6 (HGNC:27101): (phosphoinositide-3-kinase regulatory subunit 6) Phosphoinositide 3-kinase gamma is a lipid kinase that produces the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate. The kinase is composed of a catalytic subunit and one of several regulatory subunits, and is chiefly activated by G protein-coupled receptors. This gene encodes a regulatory subunit, and is distantly related to the phosphoinositide-3-kinase, regulatory subunit 5 gene which is located adjacent to this gene on chromosome 7. The orthologous protein in the mouse binds to both the catalytic subunit and to G(beta/gamma), and mediates activation of the kinase subunit downstream of G protein-coupled receptors. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010855.4. 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
	PIK3R6	NM_001010855.4	MANE Select	c.*140A>G		3_prime_UTR	Exon 20 of 20	NP_001010855.1	Q5UE93
	PIK3R6	NM_001290211.1		c.*140A>G		3_prime_UTR	Exon 20 of 20	NP_001277140.1	B3KRK9
	PIK3R6	NR_110865.1		n.2881A>G		non_coding_transcript_exon	Exon 20 of 20

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3R6	ENST00000619866.5	TSL:5 MANE Select	c.*140A>G		3_prime_UTR	Exon 20 of 20	ENSP00000480157.1	Q5UE93
	PIK3R6	ENST00000907451.1		c.*140A>G		3_prime_UTR	Exon 20 of 20	ENSP00000577510.1
	PIK3R6	ENST00000907452.1		c.*140A>G		3_prime_UTR	Exon 20 of 20	ENSP00000577511.1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53222 AN: 151964 Hom.: 11447 Cov.: 32

Gnomad AFR AF: 0.0944

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.354

GnomAD4 exome AF: 0.447 AC: 430898 AN: 964978 Hom.: 98291 Cov.: 13 AF XY: 0.447 AC XY: 216772 AN XY: 485448

African (AFR) AF: 0.0822 AC: 1824 AN: 22196

American (AMR) AF: 0.396 AC: 10008 AN: 25300

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 6709 AN: 17500

East Asian (EAS) AF: 0.384 AC: 13414 AN: 34892

South Asian (SAS) AF: 0.428 AC: 25899 AN: 60454

European-Finnish (FIN) AF: 0.528 AC: 23179 AN: 43872

Middle Eastern (MID) AF: 0.345 AC: 1014 AN: 2938

European-Non Finnish (NFE) AF: 0.463 AC: 330857 AN: 714766

Other (OTH) AF: 0.418 AC: 17994 AN: 43060

GnomAD4 genome AF: 0.350 AC: 53236 AN: 152082 Hom.: 11458 Cov.: 32 AF XY: 0.357 AC XY: 26496 AN XY: 74322

African (AFR) AF: 0.0943 AC: 3916 AN: 41538

American (AMR) AF: 0.390 AC: 5948 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1272 AN: 3470

East Asian (EAS) AF: 0.372 AC: 1920 AN: 5168

South Asian (SAS) AF: 0.430 AC: 2074 AN: 4818

European-Finnish (FIN) AF: 0.538 AC: 5678 AN: 10550

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31173 AN: 67952

Other (OTH) AF: 0.351 AC: 742 AN: 2112

Alfa AF: 0.428 Hom.: 16070

Bravo AF: 0.326

Asia WGS AF: 0.365 AC: 1267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.3
DANN	Benign	0.67
PhyloP100		0.29
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: rs2242375; hg19: chr17-8706451; COSMIC: COSV61005334; COSMIC: COSV61005334;