rs782444

Positions:

• chr3-127691098-T-C

Variant summary

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

The NM_007283.7(MGLL):​c.*1100A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 152,570 control chromosomes in the GnomAD database, including 21,092 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 0.52 (21036 hom., cov: 34)
  • Exomes 𝑓: 0.46 (56 hom.)
• Consequence: MGLL NM_007283.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.810

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 (EAS) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGLL	NM_007283.7	c.*1100A>G		3_prime_UTR_variant	8/8	ENST00000265052.10	NP_009214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGLL	ENST00000265052.10	c.*1100A>G		3_prime_UTR_variant	8/8	1	NM_007283.7	ENSP00000265052
MGLL	ENST00000398104.6	c.*1100A>G		3_prime_UTR_variant	8/8	5		ENSP00000381176	P1
MGLL	ENST00000453507.7	c.*1100A>G		3_prime_UTR_variant	7/7	2		ENSP00000404146

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79257 AN: 151928 Hom.: 21031 Cov.: 34

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.555

GnomAD4 exome AF: 0.462 AC: 242 AN: 524 Hom.: 56 Cov.: 0 AF XY: 0.500 AC XY: 163 AN XY: 326

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.435

Gnomad4 NFE exome AF: 0.608

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.521 AC: 79291 AN: 152046 Hom.: 21036 Cov.: 34 AF XY: 0.516 AC XY: 38314 AN XY: 74320

Gnomad4 AFR AF: 0.468

Gnomad4 AMR AF: 0.558

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.550

Alfa AF: 0.547 Hom.: 20210

Bravo AF: 0.531

Asia WGS AF: 0.576 AC: 2005 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	0.68
DANN	Benign	0.72

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: rs782444; hg19: chr3-127409941; COSMIC: COSV54023547; COSMIC: COSV54023547;