chr14-67599842-A-T

Position:

• chr14-67599842-A-T

Variant summary

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

The NM_004569.5(PIGH):​c.180+182T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 151,966 control chromosomes in the GnomAD database, including 12,487 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 0.40 (12487 hom., cov: 31)
• Consequence: PIGH NM_004569.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14

Genes affected

PIGH (HGNC:8964): (phosphatidylinositol glycan anchor biosynthesis class H) This gene encodes an endoplasmic reticulum associated protein that is involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI anchor is a glycolipid found on many blood cells and which serves to anchor proteins to the cell surface. The protein encoded by this gene is a subunit of the GPI N-acetylglucosaminyl (GlcNAc) transferase that transfers GlcNAc to phosphatidylinositol (PI) on the cytoplasmic side of the endoplasmic reticulum. [provided by RefSeq, Jul 2008]

GPHN (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIGH	NM_004569.5	c.180+182T>A		intron_variant		ENST00000216452.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIGH	ENST00000216452.9	c.180+182T>A		intron_variant		1	NM_004569.5	P4

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60795 AN: 151850 Hom.: 12487 Cov.: 31

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.400 AC: 60810 AN: 151966 Hom.: 12487 Cov.: 31 AF XY: 0.401 AC XY: 29754 AN XY: 74258

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.470

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.383

Alfa AF: 0.406 Hom.: 1545

Bravo AF: 0.390

Asia WGS AF: 0.391 AC: 1358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.5
DANN	Benign	0.59

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: rs2295644; hg19: chr14-68066559; COSMIC: COSV53615395;