rs17821234

chr17-1532956-G-A

Variant summary

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

The NM_006224.4(PITPNA):c.768+1143C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0887 in 152,286 control chromosomes in the GnomAD database, including 808 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 0.089 (808 hom., cov: 32)
• Consequence: PITPNA NM_006224.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890

Genes affected

PITPNA (HGNC:9001): (phosphatidylinositol transfer protein alpha) This gene encodes a member of a family of lipid-binding proteins that transfer molecules of phosphatidylinositol or phosphatidylcholine between membrane surfaces. The protein is implicated in phospholipase C signaling and in the production of phosphatidylinositol 3,4,5-trisphosphate (PIP3) by phosphoinositide-3-kinase.[provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PITPNA	NM_006224.4	c.768+1143C>T		intron_variant		ENST00000313486.12
PITPNA	XM_047436299.1	c.549+1143C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PITPNA	ENST00000313486.12	c.768+1143C>T		intron_variant		5	NM_006224.4	P1
PITPNA	ENST00000575288.5	c.*388+1143C>T		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0889 AC: 13522 AN: 152168 Hom.: 811 Cov.: 32

Gnomad AFR AF: 0.0212

Gnomad AMI AF: 0.0978

Gnomad AMR AF: 0.0834

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.0333

Gnomad FIN AF: 0.0934

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.0887 AC: 13514 AN: 152286 Hom.: 808 Cov.: 32 AF XY: 0.0854 AC XY: 6360 AN XY: 74464

Gnomad4 AFR AF: 0.0211

Gnomad4 AMR AF: 0.0833

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.0331

Gnomad4 FIN AF: 0.0934

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.107

Alfa AF: 0.107 Hom.: 117

Bravo AF: 0.0869

Asia WGS AF: 0.0850 AC: 296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	5.4
Dann	Benign	0.77

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: rs17821234; hg19: chr17-1436250; COSMIC: COSV57933046; COSMIC: COSV57933046;