rs6733143

Positions:

• chr2-46594501-G-A

Variant summary

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

The NM_002643.4(PIGF):​c.438-1918C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 151,566 control chromosomes in the GnomAD database, including 1,304 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 0.12 (1304 hom., cov: 32)
• Consequence: PIGF NM_002643.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.600

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGF	NM_002643.4	c.438-1918C>T		intron_variant		ENST00000281382.11	NP_002634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGF	ENST00000281382.11	c.438-1918C>T		intron_variant		1	NM_002643.4	ENSP00000281382.6
PIGF	ENST00000306465.8	c.438-1918C>T		intron_variant		1		ENSP00000302663.4
PIGF	ENST00000412717.1	n.*7-1918C>T		intron_variant		3		ENSP00000413202.1
PIGF	ENST00000420164.5	n.48-1918C>T		intron_variant		5		ENSP00000410361.2

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17929 AN: 151450 Hom.: 1302 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.0505

Gnomad AMR AF: 0.0955

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0404

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.0463

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.0865

Gnomad OTH AF: 0.0980

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

GnomAD4 genome AF: 0.118 AC: 17947 AN: 151566 Hom.: 1304 Cov.: 32 AF XY: 0.116 AC XY: 8571 AN XY: 74040

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.0955

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.0405

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.0463

Gnomad4 NFE AF: 0.0865

Gnomad4 OTH AF: 0.0979

Alfa AF: 0.0980 Hom.: 444

Bravo AF: 0.125

Asia WGS AF: 0.0980 AC: 342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.96
DANN	Benign	0.76

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: rs6733143; hg19: chr2-46821640;