rs2011138

Positions:

• chr3-127825086-C-A
• chr3-127825086-C-T

Variant summary

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

The variant allele was found at a frequency of 0.376 in 141,348 control chromosomes in the GnomAD database, including 9,749 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 0.38 (9749 hom., cov: 22)
• Consequence: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.714

Genes affected

(HGNC:):

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 (SAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.127825086C>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGLL	ENST00000648300.1	n.-21+580G>T		intron_variant				ENSP00000497905.1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 53175 AN: 141276 Hom.: 9750 Cov.: 22

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.376 AC: 53182 AN: 141348 Hom.: 9749 Cov.: 22 AF XY: 0.383 AC XY: 25938 AN XY: 67772

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.479

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.538

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.389

Alfa AF: 0.197 Hom.: 382

Bravo AF: 0.355

Asia WGS AF: 0.471 AC: 1638 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	0.93
DANN	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2011138; hg19: chr3-127543929; COSMIC: COSV54023682;