chr2-46593771-C-T

Variant names:

• chr2-46593771-C-T
• rs6544903
• NM_002643.4:c.438-1188G>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.438-1188G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.051 in 152,274 control chromosomes in the GnomAD database, including 285 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 0.051 (285 hom., cov: 32)
• Consequence: PIGF NM_002643.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 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.438-1188G>A		intron	N/A	NP_002634.1
	PIGF	NM_173074.3		c.438-1188G>A		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.438-1188G>A		intron	N/A	ENSP00000281382.6
	PIGF	ENST00000306465.8	TSL:1	c.438-1188G>A		intron	N/A	ENSP00000302663.4
	PIGF	ENST00000412717.1	TSL:3	n.*7-1188G>A		intron	N/A	ENSP00000413202.1

Frequencies

GnomAD3 genomes AF: 0.0510 AC: 7754 AN: 152156 Hom.: 287 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0261

Gnomad ASJ AF: 0.0734

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0352

Gnomad FIN AF: 0.0356

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0252

Gnomad OTH AF: 0.0396

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

GnomAD4 genome AF: 0.0510 AC: 7766 AN: 152274 Hom.: 285 Cov.: 32 AF XY: 0.0506 AC XY: 3764 AN XY: 74442

African (AFR) AF: 0.114 AC: 4747 AN: 41544

American (AMR) AF: 0.0260 AC: 398 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0734 AC: 255 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.0350 AC: 169 AN: 4826

European-Finnish (FIN) AF: 0.0356 AC: 378 AN: 10606

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0252 AC: 1715 AN: 68024

Other (OTH) AF: 0.0392 AC: 83 AN: 2116

Alfa AF: 0.0398 Hom.: 34

Bravo AF: 0.0520

Asia WGS AF: 0.0310 AC: 106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.25
PhyloP100		0.012
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: rs6544903; hg19: chr2-46820910;