rs1346949

Variant names:

• chr18-61980603-T-A
• rs1346949
• ENST00000639600.1:c.*1+37026A>T

Variant summary

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

The ENST00000639600.1(PIGN):​c.*1+37026A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 151,924 control chromosomes in the GnomAD database, including 7,289 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 0.31 (7289 hom., cov: 32)
• Consequence: PIGN ENST00000639600.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• multiple congenital anomalies-hypotonia-seizures syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Orphanet, ClinGen, PanelApp Australia
• Fryns syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGN	ENST00000639600.1	c.*1+37026A>T		intron_variant	Intron 24 of 24	5		ENSP00000492474.1

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46486 AN: 151806 Hom.: 7286 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.324

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

GnomAD4 genome AF: 0.306 AC: 46510 AN: 151924 Hom.: 7289 Cov.: 32 AF XY: 0.305 AC XY: 22650 AN XY: 74240

African (AFR) AF: 0.287 AC: 11887 AN: 41388

American (AMR) AF: 0.265 AC: 4043 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1089 AN: 3466

East Asian (EAS) AF: 0.356 AC: 1839 AN: 5166

South Asian (SAS) AF: 0.289 AC: 1389 AN: 4812

European-Finnish (FIN) AF: 0.345 AC: 3637 AN: 10538

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21565 AN: 67980

Other (OTH) AF: 0.329 AC: 696 AN: 2114

Alfa AF: 0.314 Hom.: 1070

Bravo AF: 0.302

Asia WGS AF: 0.319 AC: 1109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.6
DANN	Benign	0.83
PhyloP100		-0.14

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1346949; hg19: chr18-59647836;