6-24460451-T-C

Variant names:

• chr6-24460451-T-C
• rs2793434
• NM_001503.4:c.888-52A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GPLD1	NM_001503.4	c.888-52A>G		intron_variant	Intron 11 of 24	ENST00000230036.2	NP_001494.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPLD1	ENST00000230036.2	c.888-52A>G		intron_variant	Intron 11 of 24	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

GnomAD2 exomes AF: 0.431 AC: 103999 AN: 241456 AF XY: 0.440

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 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

African (AFR) AF: 0.354 AC: 11411 AN: 32270

American (AMR) AF: 0.326 AC: 13453 AN: 41314

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 16392 AN: 25642

East Asian (EAS) AF: 0.396 AC: 15629 AN: 39466

South Asian (SAS) AF: 0.445 AC: 37563 AN: 84476

European-Finnish (FIN) AF: 0.376 AC: 19068 AN: 50728

Middle Eastern (MID) AF: 0.480 AC: 2423 AN: 5052

European-Non Finnish (NFE) AF: 0.459 AC: 503404 AN: 1097148

Other (OTH) AF: 0.448 AC: 26528 AN: 59274

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

African (AFR) AF: 0.353 AC: 14640 AN: 41466

American (AMR) AF: 0.397 AC: 6051 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2221 AN: 3466

East Asian (EAS) AF: 0.380 AC: 1965 AN: 5174

South Asian (SAS) AF: 0.439 AC: 2118 AN: 4826

European-Finnish (FIN) AF: 0.363 AC: 3833 AN: 10558

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.468 AC: 31824 AN: 67972

Other (OTH) AF: 0.436 AC: 919 AN: 2106

Alfa AF: 0.458 Hom.: 47174

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
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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