Genetic Variant PIGF:c.438-1080C>G (chr2-46593663-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002643.4(PIGF):c.438-1080C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 151,994 control chromosomes in the GnomAD database, including 4,143 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 0.18 ( 4143 hom., cov: 32)

Consequence

PIGF
NM_002643.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0400

Publications

3 publications found

Variant links:

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]

PIGF Gene-Disease associations (from GenCC):

onychodystrophy, osteodystrophy, impaired intellectual development, and seizures syndrome
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

PIGF links:

LOC124906003 (HGNC:):

LOC124906003 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGF	NM_002643.4 link	c.438-1080C>G		intron_variant	Intron 4 of 5	ENST00000281382.11	NP_002634.1	Q07326-1Q6IB04

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PIGF	ENST00000281382.11 link	c.438-1080C>G	intron_variant	Intron 4 of 5	1	NM_002643.4	ENSP00000281382.6	Q07326-1
PIGF	ENST00000306465.8 link	c.438-1080C>G	intron_variant	Intron 4 of 6	1		ENSP00000302663.4	Q07326-2
PIGF	ENST00000412717.1 link	n.*7-1080C>G	intron_variant	Intron 3 of 4	3		ENSP00000413202.1	F8WEN5
PIGF	ENST00000420164.6 link	n.438-1080C>G	intron_variant	Intron 3 of 5	5		ENSP00000410361.2	H7C392

Frequencies

GnomAD3 genomes

AF:

0.179

AC:

27181

AN:

151876

Hom.:

4130

Cov.:

show subpopulations

Gnomad AFR

AF:

0.419

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.119

Gnomad ASJ

AF:

0.101

Gnomad EAS

AF:

0.0399

Gnomad SAS

AF:

0.152

Gnomad FIN

AF:

0.0461

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.0874

Gnomad OTH

AF:

0.148

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

GnomAD4 genome

AF:

0.179

AC:

27231

AN:

151994

Hom.:

4143

Cov.:

AF XY:

0.173

AC XY:

12895

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.419

AC:

17296

AN:

41276

American (AMR)

AF:

0.118

AC:

1811

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.101

AC:

350

AN:

3468

East Asian (EAS)

AF:

0.0399

AC:

207

AN:

5182

South Asian (SAS)

AF:

0.151

AC:

730

AN:

4830

European-Finnish (FIN)

AF:

0.0461

AC:

489

AN:

10614

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0874

AC:

5945

AN:

68008

Other (OTH)

AF:

0.147

AC:

312

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

966

1933

2899

3866

4832

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

278

556

834

1112

1390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0483

Hom.:

Bravo

AF:

0.196

Asia WGS

AF:

0.119

AC:

413

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.74

(source)

DANN

Benign

0.55

PhyloP100

-0.040

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over