6-24494289-T-G

Variant names:

• chr6-24494289-T-G
• rs11759284
• XM_017010753.3:c.44+678A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000475417.1(GPLD1):​n.233+678A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,172 control chromosomes in the GnomAD database, including 8,638 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 0.30 (8638 hom., cov: 32)
• Consequence: GPLD1 ENST00000475417.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.559

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPLD1	XM_017010753.3	c.44+678A>C		intron_variant	Intron 1 of 25		XP_016866242.1
GPLD1	XM_047418658.1	c.44+678A>C		intron_variant	Intron 1 of 17		XP_047274614.1
GPLD1	XR_007059240.1	n.321+678A>C		intron_variant	Intron 1 of 26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPLD1	ENST00000474784.5	n.239+678A>C		intron_variant	Intron 1 of 10	5
GPLD1	ENST00000475417.1	n.233+678A>C		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46379 AN: 152054 Hom.: 8650 Cov.: 32

Gnomad AFR AF: 0.0903

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.305 AC: 46348 AN: 152172 Hom.: 8638 Cov.: 32 AF XY: 0.302 AC XY: 22468 AN XY: 74382

African (AFR) AF: 0.0900 AC: 3740 AN: 41542

American (AMR) AF: 0.328 AC: 5008 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 1636 AN: 3468

East Asian (EAS) AF: 0.289 AC: 1498 AN: 5178

South Asian (SAS) AF: 0.302 AC: 1455 AN: 4824

European-Finnish (FIN) AF: 0.326 AC: 3450 AN: 10570

Middle Eastern (MID) AF: 0.397 AC: 116 AN: 292

European-Non Finnish (NFE) AF: 0.420 AC: 28530 AN: 67996

Other (OTH) AF: 0.325 AC: 685 AN: 2110

Alfa AF: 0.386 Hom.: 20353

Bravo AF: 0.296

Asia WGS AF: 0.256 AC: 892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.67
PhyloP100		-0.56

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11759284; hg19: chr6-24494517;