rs9289321

chr3-127809926-G-Achr3-127809926-G-T

Variant summary

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

The NM_007283.7(MGLL):c.155+11768C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,116 control chromosomes in the GnomAD database, including 4,381 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 0.22 (4381 hom., cov: 32)
• Consequence: MGLL NM_007283.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390

Genes affected

MGLL (HGNC:17038): (monoglyceride lipase) This gene encodes a serine hydrolase of the AB hydrolase superfamily that catalyzes the conversion of monoacylglycerides to free fatty acids and glycerol. The encoded protein plays a critical role in several physiological processes including pain and nociperception through hydrolysis of the endocannabinoid 2-arachidonoylglycerol. Expression of this gene may play a role in cancer tumorigenesis and metastasis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MGLL	NM_007283.7	c.155+11768C>T		intron_variant		ENST00000265052.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MGLL	ENST00000265052.10	c.155+11768C>T		intron_variant		1	NM_007283.7

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33351 AN: 151998 Hom.: 4356 Cov.: 32

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.0345

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.220 AC: 33423 AN: 152116 Hom.: 4381 Cov.: 32 AF XY: 0.217 AC XY: 16123 AN XY: 74374

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.0345

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.183

Alfa AF: 0.189 Hom.: 400

Bravo AF: 0.232

Asia WGS AF: 0.128 AC: 444 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.2
Dann	Benign	0.53

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: rs9289321; hg19: chr3-127528769;