rs6544903

chr2-46593771-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIGF	NM_002643.4	c.438-1188G>A		intron_variant		ENST00000281382.11
LOC124906003	XR_007086307.1	n.414C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIGF	ENST00000281382.11	c.438-1188G>A		intron_variant		1	NM_002643.4	P1
PIGF	ENST00000306465.8	c.438-1188G>A		intron_variant		1
PIGF	ENST00000412717.1	c.*7-1188G>A		intron_variant, NMD_transcript_variant		3
PIGF	ENST00000420164.5	c.48-1188G>A		intron_variant, NMD_transcript_variant		5

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

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.0260

Gnomad4 ASJ AF: 0.0734

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0350

Gnomad4 FIN AF: 0.0356

Gnomad4 NFE AF: 0.0252

Gnomad4 OTH AF: 0.0392

Alfa AF: 0.0376 Hom.: 29

Bravo AF: 0.0520

Asia WGS AF: 0.0310 AC: 106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.2
Dann	Benign	0.25

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: rs6544903; hg19: chr2-46820910;