rs9461011

Positions:

• chr6-24440123-A-G

Variant summary

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

The NM_001503.4(GPLD1):​c.2021-2834T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,138 control chromosomes in the GnomAD database, including 3,851 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 0.22 (3851 hom., cov: 33)
• Consequence: GPLD1 NM_001503.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.883

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPLD1	NM_001503.4	c.2021-2834T>C		intron_variant		ENST00000230036.2	NP_001494.2
GPLD1	XM_017010753.3	c.2051-2834T>C		intron_variant			XP_016866242.1
GPLD1	XM_047418657.1	c.1532-2834T>C		intron_variant			XP_047274613.1
GPLD1	XR_007059240.1	n.2328-2834T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPLD1	ENST00000230036.2	c.2021-2834T>C		intron_variant		1	NM_001503.4	ENSP00000230036	P1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33262 AN: 152020 Hom.: 3845 Cov.: 33

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.0198

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.219 AC: 33290 AN: 152138 Hom.: 3851 Cov.: 33 AF XY: 0.216 AC XY: 16035 AN XY: 74366

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.0199

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.199

Alfa AF: 0.236 Hom.: 7175

Bravo AF: 0.218

Asia WGS AF: 0.124 AC: 432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.0
DANN	Benign	0.50

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: rs9461011; hg19: chr6-24440351;