16-19502819-A-G

Position:

• chr16-19502819-A-G

Variant summary

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

The NM_016641.4(GDE1):​c.*651T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 152,178 control chromosomes in the GnomAD database, including 54,753 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 0.85 (54747 hom., cov: 31)
  • Exomes 𝑓: 0.93 (6 hom.)
• Consequence: GDE1 NM_016641.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.549

Genes affected

GDE1 (HGNC:29644): (glycerophosphodiester phosphodiesterase 1) Predicted to enable glycerophosphodiester phosphodiesterase activity; glycerophosphoinositol glycerophosphodiesterase activity; and lysophospholipase activity. Predicted to be involved in N-acylethanolamine metabolic process; ethanolamine metabolic process; and phospholipid metabolic process. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDE1	NM_016641.4	c.*651T>C		3_prime_UTR_variant	6/6	ENST00000353258.8	NP_057725.1
GDE1	NM_001324066.2	c.*651T>C		3_prime_UTR_variant	6/6		NP_001310995.1
GDE1	NM_001324067.2	c.*651T>C		3_prime_UTR_variant	5/5		NP_001310996.1
GDE1	NR_136689.2	n.1813T>C		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GDE1	ENST00000353258.8	c.*651T>C		3_prime_UTR_variant	6/6	1	NM_016641.4	ENSP00000261386	P1
GDE1	ENST00000564172.1	c.*1316T>C		3_prime_UTR_variant, NMD_transcript_variant	6/6	1		ENSP00000457431

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128873 AN: 152046 Hom.: 54695 Cov.: 31

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.905

Gnomad FIN AF: 0.896

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.856

Gnomad OTH AF: 0.827

GnomAD4 exome AF: 0.929 AC: 13 AN: 14 Hom.: 6 Cov.: 0 AF XY: 0.917 AC XY: 11 AN XY: 12

Gnomad4 NFE exome AF: 0.917

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.848 AC: 128980 AN: 152164 Hom.: 54747 Cov.: 31 AF XY: 0.849 AC XY: 63136 AN XY: 74386

Gnomad4 AFR AF: 0.838

Gnomad4 AMR AF: 0.805

Gnomad4 ASJ AF: 0.783

Gnomad4 EAS AF: 0.833

Gnomad4 SAS AF: 0.906

Gnomad4 FIN AF: 0.896

Gnomad4 NFE AF: 0.856

Gnomad4 OTH AF: 0.830

Alfa AF: 0.847 Hom.: 56433

Bravo AF: 0.837

Asia WGS AF: 0.873 AC: 3036 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	8.6
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2521795; hg19: chr16-19514141;