rs17818399

Positions:

• chr2-46598887-A-C
• chr2-46598887-A-G

Variant summary

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

The NM_002643.4(PIGF):​c.438-6304T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,164 control chromosomes in the GnomAD database, including 6,744 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 0.29 (6744 hom., cov: 32)
• Consequence: PIGF NM_002643.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.941

Genes affected

PIGF (HGNC:8962): (phosphatidylinositol glycan anchor biosynthesis class F) This gene encodes a protein involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor, a glycolipid containing three mannose molecules in its core backbone, is found on many blood cells where it serves to anchor proteins to the cell surface. The encoded protein and another GPI synthesis protein, PIGO, function in the transfer of ethanolaminephosphate to the third mannose in GPI. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

LOC124906003 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIGF	NM_002643.4	c.438-6304T>G		intron_variant		ENST00000281382.11
LOC124906003	XR_007086307.1	n.2880-1707A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIGF	ENST00000281382.11	c.438-6304T>G		intron_variant		1	NM_002643.4	P1
PIGF	ENST00000306465.8	c.438-6304T>G		intron_variant		1
PIGF	ENST00000412717.1	c.*7-6304T>G		intron_variant, NMD_transcript_variant		3
PIGF	ENST00000420164.5	c.48-6304T>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44405 AN: 152046 Hom.: 6740 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.292 AC: 44433 AN: 152164 Hom.: 6744 Cov.: 32 AF XY: 0.291 AC XY: 21663 AN XY: 74394

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.289

Alfa AF: 0.225 Hom.: 822

Bravo AF: 0.290

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.7
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: rs17818399; hg19: chr2-46826026;