rs3773155

Positions:

• chr3-127719685-A-G

Variant summary

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

The NM_007283.7(MGLL):​c.510+1368T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,084 control chromosomes in the GnomAD database, including 3,030 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 0.18 (3030 hom., cov: 32)
• Consequence: MGLL NM_007283.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.44

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGLL	NM_007283.7	c.510+1368T>C		intron_variant		ENST00000265052.10	NP_009214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGLL	ENST00000265052.10	c.510+1368T>C		intron_variant		1	NM_007283.7	ENSP00000265052

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27306 AN: 151966 Hom.: 3033 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.0663

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.180 AC: 27328 AN: 152084 Hom.: 3030 Cov.: 32 AF XY: 0.175 AC XY: 12996 AN XY: 74370

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.0663

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.157

Alfa AF: 0.136 Hom.: 1449

Bravo AF: 0.190

Asia WGS AF: 0.198 AC: 690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.7
DANN	Benign	0.059

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: rs3773155; hg19: chr3-127438528;