rs6733143

Variant names:

• chr2-46594501-G-A
• rs6733143
• NM_002643.4:c.438-1918C>T

Variant summary

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

The NM_002643.4(PIGF):​c.438-1918C>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
• Publications: 5 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002643.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGF	NM_002643.4	MANE Select	c.438-1918C>T		intron	N/A	NP_002634.1
	PIGF	NM_173074.3		c.438-1918C>T		intron	N/A	NP_775097.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGF	ENST00000281382.11	TSL:1 MANE Select	c.438-1918C>T		intron	N/A	ENSP00000281382.6
	PIGF	ENST00000306465.8	TSL:1	c.438-1918C>T		intron	N/A	ENSP00000302663.4
	PIGF	ENST00000412717.1	TSL:3	n.*7-1918C>T		intron	N/A	ENSP00000413202.1

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

African (AFR) AF: 0.207 AC: 8565 AN: 41298

American (AMR) AF: 0.0955 AC: 1452 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 350 AN: 3466

East Asian (EAS) AF: 0.0405 AC: 208 AN: 5132

South Asian (SAS) AF: 0.151 AC: 724 AN: 4800

European-Finnish (FIN) AF: 0.0463 AC: 484 AN: 10450

Middle Eastern (MID) AF: 0.127 AC: 37 AN: 292

European-Non Finnish (NFE) AF: 0.0865 AC: 5875 AN: 67906

Other (OTH) AF: 0.0979 AC: 206 AN: 2104

Alfa AF: 0.102 Hom.: 1807

Bravo AF: 0.125

Asia WGS AF: 0.0980 AC: 342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.96
DANN	Benign	0.76
PhyloP100		-0.60
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: rs6733143; hg19: chr2-46821640;