rs11715363

Positions:

• chr3-127797141-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.156-15246A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 151,906 control chromosomes in the GnomAD database, including 4,163 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 (4163 hom., cov: 32)
• Consequence: MGLL NM_007283.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.448

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGLL	NM_007283.7	c.156-15246A>G		intron_variant		ENST00000265052.10	NP_009214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGLL	ENST00000265052.10	c.156-15246A>G		intron_variant		1	NM_007283.7	ENSP00000265052

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33703 AN: 151786 Hom.: 4154 Cov.: 32

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.222 AC: 33754 AN: 151906 Hom.: 4163 Cov.: 32 AF XY: 0.221 AC XY: 16418 AN XY: 74222

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.193

Alfa AF: 0.185 Hom.: 5540

Bravo AF: 0.232

Asia WGS AF: 0.249 AC: 866 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.48

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: rs11715363; hg19: chr3-127515984;