rs16889393

Positions:

• chr6-24494235-G-A
• chr6-24494235-G-T

Variant summary

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

The XM_017010753.3(GPLD1):​c.44+732C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0294 in 152,238 control chromosomes in the GnomAD database, including 112 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 0.029 (112 hom., cov: 33)
• Consequence: GPLD1 XM_017010753.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPLD1	XM_017010753.3	c.44+732C>T		intron_variant			XP_016866242.1
GPLD1	XM_047418658.1	c.44+732C>T		intron_variant			XP_047274614.1
GPLD1	XR_007059240.1	n.321+732C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPLD1	ENST00000474784.5	n.239+732C>T		intron_variant, non_coding_transcript_variant		5
GPLD1	ENST00000475417.1	n.233+732C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0293 AC: 4463 AN: 152120 Hom.: 111 Cov.: 33

Gnomad AFR AF: 0.0237

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0280

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.0834

Gnomad SAS AF: 0.0987

Gnomad FIN AF: 0.0165

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0252

Gnomad OTH AF: 0.0321

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

GnomAD4 genome AF: 0.0294 AC: 4473 AN: 152238 Hom.: 112 Cov.: 33 AF XY: 0.0298 AC XY: 2220 AN XY: 74434

Gnomad4 AFR AF: 0.0237

Gnomad4 AMR AF: 0.0279

Gnomad4 ASJ AF: 0.0268

Gnomad4 EAS AF: 0.0838

Gnomad4 SAS AF: 0.0979

Gnomad4 FIN AF: 0.0165

Gnomad4 NFE AF: 0.0252

Gnomad4 OTH AF: 0.0375

Alfa AF: 0.0246 Hom.: 58

Bravo AF: 0.0293

Asia WGS AF: 0.106 AC: 370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.60
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16889393; hg19: chr6-24494463;