rs793687

Positions:

• chr6-24430830-G-T

Variant summary

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

The NM_001503.4(GPLD1):​c.2437-1712C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 151,944 control chromosomes in the GnomAD database, including 28,992 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 0.61 (28992 hom., cov: 32)
• Consequence: GPLD1 NM_001503.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.781

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPLD1	NM_001503.4	c.2437-1712C>A		intron_variant		ENST00000230036.2	NP_001494.2
GPLD1	XM_017010753.3	c.2467-1712C>A		intron_variant			XP_016866242.1
GPLD1	XM_047418657.1	c.1948-1712C>A		intron_variant			XP_047274613.1
GPLD1	XR_007059240.1	n.2744-1712C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPLD1	ENST00000230036.2	c.2437-1712C>A		intron_variant		1	NM_001503.4	ENSP00000230036	P1
GPLD1	ENST00000492917.2	n.312-1712C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92869 AN: 151826 Hom.: 28988 Cov.: 32

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.611

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

GnomAD4 genome AF: 0.611 AC: 92901 AN: 151944 Hom.: 28992 Cov.: 32 AF XY: 0.604 AC XY: 44860 AN XY: 74246

Gnomad4 AFR AF: 0.564

Gnomad4 AMR AF: 0.563

Gnomad4 ASJ AF: 0.719

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.585

Gnomad4 NFE AF: 0.681

Gnomad4 OTH AF: 0.605

Alfa AF: 0.652 Hom.: 4070

Bravo AF: 0.606

Asia WGS AF: 0.396 AC: 1377 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.9
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs793687; hg19: chr6-24431058;