chr2-46593663-G-C

Position:

• chr2-46593663-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000281382.11(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 ENST00000281382.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400

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=-0.89).
• 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/exons	MANE	Protein	UniProt
PIGF	NM_002643.4	c.438-1080C>G		intron_variant		ENST00000281382.11	NP_002634.1
LOC124906003	XR_007086307.1	n.306G>C		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGF	ENST00000281382.11	c.438-1080C>G		intron_variant		1	NM_002643.4	ENSP00000281382	P1
PIGF	ENST00000306465.8	c.438-1080C>G		intron_variant		1		ENSP00000302663
PIGF	ENST00000412717.1	c.*7-1080C>G		intron_variant, NMD_transcript_variant		3		ENSP00000413202
PIGF	ENST00000420164.5	c.48-1080C>G		intron_variant, NMD_transcript_variant		5		ENSP00000410361

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27181 AN: 151876 Hom.: 4130 Cov.: 32

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.: 32 AF XY: 0.173 AC XY: 12895 AN XY: 74344

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.0399

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.0461

Gnomad4 NFE AF: 0.0874

Gnomad4 OTH AF: 0.147

Alfa AF: 0.0483 Hom.: 59

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
DANN	Benign	0.55

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: rs3768725; hg19: chr2-46820802;