chr6-24444903-T-C

Position:

• chr6-24444903-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.2020+643A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.926 in 152,200 control chromosomes in the GnomAD database, including 65,401 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 0.93 (65401 hom., cov: 31)
• Consequence: GPLD1 NM_001503.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.200

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 = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPLD1	NM_001503.4	c.2020+643A>G		intron_variant		ENST00000230036.2	NP_001494.2
GPLD1	XM_017010753.3	c.2050+643A>G		intron_variant			XP_016866242.1
GPLD1	XM_047418657.1	c.1531+643A>G		intron_variant			XP_047274613.1
GPLD1	XR_007059240.1	n.2327+643A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPLD1	ENST00000230036.2	c.2020+643A>G		intron_variant		1	NM_001503.4	ENSP00000230036.1

Frequencies

GnomAD3 genomes AF: 0.927 AC: 140923 AN: 152082 Hom.: 65375 Cov.: 31

Gnomad AFR AF: 0.885

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.930

Gnomad ASJ AF: 0.931

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.876

Gnomad FIN AF: 0.963

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.954

Gnomad OTH AF: 0.923

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

GnomAD4 genome AF: 0.926 AC: 141003 AN: 152200 Hom.: 65401 Cov.: 31 AF XY: 0.926 AC XY: 68888 AN XY: 74398

Gnomad4 AFR AF: 0.885

Gnomad4 AMR AF: 0.930

Gnomad4 ASJ AF: 0.931

Gnomad4 EAS AF: 0.867

Gnomad4 SAS AF: 0.876

Gnomad4 FIN AF: 0.963

Gnomad4 NFE AF: 0.954

Gnomad4 OTH AF: 0.918

Alfa AF: 0.946 Hom.: 88905

Bravo AF: 0.923

Asia WGS AF: 0.860 AC: 2991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.68

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: rs793715; hg19: chr6-24445131;