rs9461011

Variant names:

• chr6-24440123-A-G
• rs9461011
• NM_001503.4:c.2021-2834T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.95).
• 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 rank	MANE	Protein	UniProt
GPLD1	NM_001503.4	c.2021-2834T>C		intron_variant	Intron 20 of 24	ENST00000230036.2	NP_001494.2
GPLD1	XM_017010753.3	c.2051-2834T>C		intron_variant	Intron 21 of 25		XP_016866242.1
GPLD1	XM_047418657.1	c.1532-2834T>C		intron_variant	Intron 15 of 19		XP_047274613.1
GPLD1	XR_007059240.1	n.2328-2834T>C		intron_variant	Intron 21 of 26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPLD1	ENST00000230036.2	c.2021-2834T>C		intron_variant	Intron 20 of 24	1	NM_001503.4	ENSP00000230036.1

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

African (AFR) AF: 0.200 AC: 8317 AN: 41508

American (AMR) AF: 0.226 AC: 3445 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 535 AN: 3470

East Asian (EAS) AF: 0.0199 AC: 103 AN: 5186

South Asian (SAS) AF: 0.186 AC: 896 AN: 4822

European-Finnish (FIN) AF: 0.223 AC: 2356 AN: 10576

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16883 AN: 67990

Other (OTH) AF: 0.199 AC: 420 AN: 2110

Alfa AF: 0.235 Hom.: 16865

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
PhyloP100		-0.88
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: rs9461011; hg19: chr6-24440351;