rs4646829

Positions:

• chr6-24494776-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The XM_017010753.3(GPLD1):​c.44+191G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0287 in 436,896 control chromosomes in the GnomAD database, including 297 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.036 (189 hom., cov: 33)
  • Exomes 𝑓: 0.025 (108 hom.)
• Consequence: GPLD1 XM_017010753.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.85

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 6-24494776-C-T is Benign according to our data. Variant chr6-24494776-C-T is described in ClinVar as [Benign]. Clinvar id is 1233201.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPLD1	XM_017010753.3	c.44+191G>A		intron_variant			XP_016866242.1
GPLD1	XM_047418658.1	c.44+191G>A		intron_variant			XP_047274614.1
GPLD1	XR_007059240.1	n.321+191G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPLD1	ENST00000474784.5	n.239+191G>A		intron_variant, non_coding_transcript_variant		5
GPLD1	ENST00000475417.1	n.233+191G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0358 AC: 5441 AN: 152172 Hom.: 187 Cov.: 33

Gnomad AFR AF: 0.0785

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0164

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.00753

Gnomad SAS AF: 0.0310

Gnomad FIN AF: 0.00471

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0229

Gnomad OTH AF: 0.0320

GnomAD4 exome AF: 0.0248 AC: 7069 AN: 284606 Hom.: 108 AF XY: 0.0243 AC XY: 3464 AN XY: 142816

Gnomad4 AFR exome AF: 0.0870

Gnomad4 AMR exome AF: 0.0162

Gnomad4 ASJ exome AF: 0.0174

Gnomad4 EAS exome AF: 0.0254

Gnomad4 SAS exome AF: 0.0279

Gnomad4 FIN exome AF: 0.00469

Gnomad4 NFE exome AF: 0.0247

Gnomad4 OTH exome AF: 0.0268

GnomAD4 genome AF: 0.0358 AC: 5449 AN: 152290 Hom.: 189 Cov.: 33 AF XY: 0.0341 AC XY: 2536 AN XY: 74460

Gnomad4 AFR AF: 0.0786

Gnomad4 AMR AF: 0.0164

Gnomad4 ASJ AF: 0.0176

Gnomad4 EAS AF: 0.00755

Gnomad4 SAS AF: 0.0308

Gnomad4 FIN AF: 0.00471

Gnomad4 NFE AF: 0.0229

Gnomad4 OTH AF: 0.0312

Alfa AF: 0.0288 Hom.: 5

Bravo AF: 0.0387

Asia WGS AF: 0.0180 AC: 64 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.0
DANN	Benign	0.93

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4646829; hg19: chr6-24495004;