6-24444903-T-C

Variant names:

• chr6-24444903-T-C
• rs793715
• NM_001503.4:c.2020+643A>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.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
• Publications: 3 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 = 0.948 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001503.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPLD1	NM_001503.4	MANE Select	c.2020+643A>G		intron	N/A	NP_001494.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPLD1	ENST00000230036.2	TSL:1 MANE Select	c.2020+643A>G		intron	N/A	ENSP00000230036.1	P80108-1
	GPLD1	ENST00000891936.1		c.2062+643A>G		intron	N/A	ENSP00000561995.1
	GPLD1	ENST00000891937.1		c.2020+643A>G		intron	N/A	ENSP00000561996.1

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

African (AFR) AF: 0.885 AC: 36707 AN: 41500

American (AMR) AF: 0.930 AC: 14221 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.931 AC: 3234 AN: 3472

East Asian (EAS) AF: 0.867 AC: 4489 AN: 5176

South Asian (SAS) AF: 0.876 AC: 4222 AN: 4818

European-Finnish (FIN) AF: 0.963 AC: 10203 AN: 10596

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.954 AC: 64892 AN: 68032

Other (OTH) AF: 0.918 AC: 1943 AN: 2116

Alfa AF: 0.944 Hom.: 122584

Bravo AF: 0.923

Asia WGS AF: 0.860 AC: 2991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.68
PhyloP100		0.20
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: rs793715; hg19: chr6-24445131;