rs7098785

chr10-96658173-A-G

Variant summary

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

The NM_152309.3(PIK3AP1):c.431-1239T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 152,026 control chromosomes in the GnomAD database, including 32,436 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 0.64 (32436 hom., cov: 31)
• Consequence: PIK3AP1 NM_152309.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.41

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3AP1	NM_152309.3	c.431-1239T>C		intron_variant		ENST00000339364.10
PIK3AP1	XM_005269499.2	c.-104-1239T>C		intron_variant
PIK3AP1	XM_011539248.2	c.431-1239T>C		intron_variant
PIK3AP1	XM_047424566.1	c.-104-1239T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3AP1	ENST00000339364.10	c.431-1239T>C		intron_variant		1	NM_152309.3	P1
PIK3AP1	ENST00000371110.6	c.-104-1239T>C		intron_variant		2
PIK3AP1	ENST00000468783.1	n.77-1239T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96521 AN: 151910 Hom.: 32385 Cov.: 31

Gnomad AFR AF: 0.870

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.636 AC: 96627 AN: 152026 Hom.: 32436 Cov.: 31 AF XY: 0.632 AC XY: 46955 AN XY: 74308

Gnomad4 AFR AF: 0.870

Gnomad4 AMR AF: 0.645

Gnomad4 ASJ AF: 0.592

Gnomad4 EAS AF: 0.627

Gnomad4 SAS AF: 0.609

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.521

Gnomad4 OTH AF: 0.634

Alfa AF: 0.562 Hom.: 33903

Bravo AF: 0.660

Asia WGS AF: 0.658 AC: 2290 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.12
Dann	Benign	0.44

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: rs7098785; hg19: chr10-98417930;