rs687528

Positions:

• chr10-96673848-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152309.3(PIK3AP1):​c.431-16914C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 152,042 control chromosomes in the GnomAD database, including 27,810 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 0.58 (27810 hom., cov: 32)
• Consequence: PIK3AP1 NM_152309.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900

Genes affected

PIK3AP1 (HGNC:30034): (phosphoinositide-3-kinase adaptor protein 1) Predicted to enable phosphatidylinositol 3-kinase regulatory subunit binding activity and signaling receptor binding activity. Predicted to be involved in regulation of inflammatory response; regulation of signal transduction; and toll-like receptor signaling pathway. Predicted to be located in cytoplasm and membrane. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3AP1	NM_152309.3	c.431-16914C>G		intron_variant		ENST00000339364.10	NP_689522.2
PIK3AP1	XM_005269499.2	c.-104-16914C>G		intron_variant			XP_005269556.1
PIK3AP1	XM_011539248.2	c.431-16914C>G		intron_variant			XP_011537550.1
PIK3AP1	XM_047424566.1	c.-104-16914C>G		intron_variant			XP_047280522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3AP1	ENST00000339364.10	c.431-16914C>G		intron_variant		1	NM_152309.3	ENSP00000339826	P1
PIK3AP1	ENST00000468783.1	n.77-16914C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87466 AN: 151924 Hom.: 27755 Cov.: 32

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.663

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.576 AC: 87579 AN: 152042 Hom.: 27810 Cov.: 32 AF XY: 0.571 AC XY: 42410 AN XY: 74320

Gnomad4 AFR AF: 0.861

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.548

Gnomad4 EAS AF: 0.560

Gnomad4 SAS AF: 0.534

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.579

Alfa AF: 0.497 Hom.: 2590

Bravo AF: 0.606

Asia WGS AF: 0.597 AC: 2079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.9
DANN	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs687528; hg19: chr10-98433605;