chr2-46593929-A-T

Variant names:

• chr2-46593929-A-T
• rs3768723
• NM_002643.4:c.438-1346T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002643.4(PIGF):​c.438-1346T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,130 control chromosomes in the GnomAD database, including 4,937 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 0.23 (4937 hom., cov: 32)
• Consequence: PIGF NM_002643.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.352
• Publications: 4 publications found

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)

LOC124906003 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGF	NM_002643.4	c.438-1346T>A		intron_variant	Intron 4 of 5	ENST00000281382.11	NP_002634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGF	ENST00000281382.11	c.438-1346T>A		intron_variant	Intron 4 of 5	1	NM_002643.4	ENSP00000281382.6
PIGF	ENST00000306465.8	c.438-1346T>A		intron_variant	Intron 4 of 6	1		ENSP00000302663.4
PIGF	ENST00000412717.1	n.*7-1346T>A		intron_variant	Intron 3 of 4	3		ENSP00000413202.1
PIGF	ENST00000420164.6	n.438-1346T>A		intron_variant	Intron 3 of 5	5		ENSP00000410361.2

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35270 AN: 152012 Hom.: 4924 Cov.: 32

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.0404

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.232 AC: 35322 AN: 152130 Hom.: 4937 Cov.: 32 AF XY: 0.225 AC XY: 16766 AN XY: 74372

African (AFR) AF: 0.396 AC: 16417 AN: 41450

American (AMR) AF: 0.154 AC: 2349 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 470 AN: 3470

East Asian (EAS) AF: 0.0405 AC: 210 AN: 5190

South Asian (SAS) AF: 0.169 AC: 815 AN: 4822

European-Finnish (FIN) AF: 0.147 AC: 1553 AN: 10580

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12969 AN: 68008

Other (OTH) AF: 0.191 AC: 405 AN: 2116

Alfa AF: 0.207 Hom.: 473

Bravo AF: 0.240

Asia WGS AF: 0.126 AC: 440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.45
DANN	Benign	0.49
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3768723; hg19: chr2-46821068;