16-19513549-A-G

Variant names:

• chr16-19513549-A-G
• rs11640077
• NM_016641.4:c.438-2605T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016641.4(GDE1):​c.438-2605T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,966 control chromosomes in the GnomAD database, including 11,636 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 0.36 (11636 hom., cov: 32)
• Consequence: GDE1 NM_016641.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.18
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016641.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDE1	NM_016641.4	MANE Select	c.438-2605T>C		intron	N/A	NP_057725.1
	GDE1	NM_001324067.2		c.438-2605T>C		intron	N/A	NP_001310996.1
	GDE1	NM_001324066.2		c.108-2605T>C		intron	N/A	NP_001310995.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDE1	ENST00000353258.8	TSL:1 MANE Select	c.438-2605T>C		intron	N/A	ENSP00000261386.3
	GDE1	ENST00000564172.1	TSL:1	n.*107-2605T>C		intron	N/A	ENSP00000457431.1
	GDE1	ENST00000858770.1		c.438-2605T>C		intron	N/A	ENSP00000528829.1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55249 AN: 151848 Hom.: 11606 Cov.: 32

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.364 AC: 55322 AN: 151966 Hom.: 11636 Cov.: 32 AF XY: 0.364 AC XY: 27013 AN XY: 74278

African (AFR) AF: 0.548 AC: 22686 AN: 41410

American (AMR) AF: 0.455 AC: 6946 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1111 AN: 3470

East Asian (EAS) AF: 0.558 AC: 2875 AN: 5154

South Asian (SAS) AF: 0.236 AC: 1138 AN: 4830

European-Finnish (FIN) AF: 0.201 AC: 2118 AN: 10560

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17426 AN: 67964

Other (OTH) AF: 0.365 AC: 772 AN: 2114

Alfa AF: 0.251 Hom.: 944

Bravo AF: 0.396

Asia WGS AF: 0.381 AC: 1325 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.82
DANN	Benign	0.43
PhyloP100		-3.2
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: rs11640077; hg19: chr16-19524871;