rs936839

chr3-127780135-C-T

Variant summary

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

The NM_007283.7(MGLL):c.262+1654G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0504 in 152,244 control chromosomes in the GnomAD database, including 298 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 0.050 (298 hom., cov: 33)
• Consequence: MGLL NM_007283.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.924

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=-0.58).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MGLL	NM_007283.7	c.262+1654G>A		intron_variant		ENST00000265052.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MGLL	ENST00000265052.10	c.262+1654G>A		intron_variant		1	NM_007283.7

Frequencies

GnomAD3 genomes AF: 0.0504 AC: 7671 AN: 152126 Hom.: 299 Cov.: 33

Gnomad AFR AF: 0.0436

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0246

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.0129

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.0908

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0486

Gnomad OTH AF: 0.0335

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

GnomAD4 genome AF: 0.0504 AC: 7678 AN: 152244 Hom.: 298 Cov.: 33 AF XY: 0.0541 AC XY: 4031 AN XY: 74442

Gnomad4 AFR AF: 0.0438

Gnomad4 AMR AF: 0.0245

Gnomad4 ASJ AF: 0.0196

Gnomad4 EAS AF: 0.0129

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.0908

Gnomad4 NFE AF: 0.0486

Gnomad4 OTH AF: 0.0327

Alfa AF: 0.0477 Hom.: 316

Bravo AF: 0.0408

Asia WGS AF: 0.109 AC: 378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	14
Dann	Benign	0.84

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: rs936839; hg19: chr3-127498978;