18-62094423-C-T

Position:

• chr18-62094423-C-T

Variant summary

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

The NM_176787.5(PIGN):​c.2180+1425G>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 151,982 control chromosomes in the GnomAD database, including 4,239 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 (4239 hom., cov: 32)
• Consequence: PIGN NM_176787.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124

Genes affected

PIGN (HGNC:8967): (phosphatidylinositol glycan anchor biosynthesis class N) This gene encodes a protein that is involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor is a glycolipid found on many blood cells and serves to anchor proteins to the cell surface. This protein is expressed in the endoplasmic reticulum and transfers phosphoethanolamine (EtNP) to the first mannose of the GPI anchor. Two alternatively spliced variants, which encode an identical isoform, have been reported. [provided by RefSeq, Jul 2008]

PIGN (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGN	NM_176787.5	c.2180+1425G>A		intron_variant		ENST00000640252.2	NP_789744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGN	ENST00000640252.2	c.2180+1425G>A		intron_variant		1	NM_176787.5	ENSP00000492233.1
PIGN	ENST00000400334.7	c.2180+1425G>A		intron_variant		1		ENSP00000383188.2
PIGN	ENST00000638424.1	n.2180+1425G>A		intron_variant		5		ENSP00000491963.1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35184 AN: 151864 Hom.: 4234 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.0911

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.232 AC: 35197 AN: 151982 Hom.: 4239 Cov.: 32 AF XY: 0.230 AC XY: 17073 AN XY: 74278

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.0915

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.238

Alfa AF: 0.252 Hom.: 1946

Bravo AF: 0.225

Asia WGS AF: 0.148 AC: 513 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.5
DANN	Benign	0.78

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: rs677295; hg19: chr18-59761656;