6-24460451-T-C

Position:

• chr6-24460451-T-C

Variant summary

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

The NM_001503.4(GPLD1):​c.888-52A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 1,587,380 control chromosomes in the GnomAD database, including 161,040 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 0.42 (13818 hom., cov: 32)
  • Exomes 𝑓: 0.45 (147222 hom.)
• Consequence: GPLD1 NM_001503.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.535

Genes affected

GPLD1 (HGNC:4459): (glycosylphosphatidylinositol specific phospholipase D1) Many proteins are tethered to the extracellular face of eukaryotic plasma membranes by a glycosylphosphatidylinositol (GPI) anchor. The GPI-anchor is a glycolipid found on many blood cells. The protein encoded by this gene is a GPI degrading enzyme. Glycosylphosphatidylinositol specific phospholipase D1 hydrolyzes the inositol phosphate linkage in proteins anchored by phosphatidylinositol glycans, thereby releasing the attached protein from the plasma membrane. [provided by RefSeq, Jul 2008]

GPLD1 (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 (NFE) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPLD1	NM_001503.4	c.888-52A>G		intron_variant		ENST00000230036.2	NP_001494.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPLD1	ENST00000230036.2	c.888-52A>G		intron_variant		1	NM_001503.4	ENSP00000230036.1

Frequencies

GnomAD3 genomes AF: 0.421 AC: 64000 AN: 151892 Hom.: 13826 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.435

GnomAD3 exomes AF: 0.431 AC: 103999 AN: 241456 Hom.: 23204 AF XY: 0.440 AC XY: 57781 AN XY: 131214

Gnomad AFR exome AF: 0.355

Gnomad AMR exome AF: 0.312

Gnomad ASJ exome AF: 0.641

Gnomad EAS exome AF: 0.382

Gnomad SAS exome AF: 0.442

Gnomad FIN exome AF: 0.370

Gnomad NFE exome AF: 0.471

Gnomad OTH exome AF: 0.458

GnomAD4 exome AF: 0.450 AC: 645871 AN: 1435370 Hom.: 147222 Cov.: 25 AF XY: 0.452 AC XY: 323467 AN XY: 715068

Gnomad4 AFR exome AF: 0.354

Gnomad4 AMR exome AF: 0.326

Gnomad4 ASJ exome AF: 0.639

Gnomad4 EAS exome AF: 0.396

Gnomad4 SAS exome AF: 0.445

Gnomad4 FIN exome AF: 0.376

Gnomad4 NFE exome AF: 0.459

Gnomad4 OTH exome AF: 0.448

GnomAD4 genome AF: 0.421 AC: 64004 AN: 152010 Hom.: 13818 Cov.: 32 AF XY: 0.417 AC XY: 30970 AN XY: 74288

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.641

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.436

Alfa AF: 0.468 Hom.: 31432

Bravo AF: 0.418

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.69
DANN	Benign	0.24

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: rs2793434; hg19: chr6-24460679; COSMIC: COSV57759902;