3-127740911-A-T

Variant names:

• chr3-127740911-A-T
• rs9759081
• NM_007283.7:c.263-18345T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007283.7(MGLL):​c.263-18345T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,164 control chromosomes in the GnomAD database, including 4,559 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 0.24 (4559 hom., cov: 33)
• Consequence: MGLL NM_007283.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.54
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007283.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGLL	NM_007283.7	MANE Select	c.263-18345T>A		intron	N/A	NP_009214.1	A0A0C4DFN3
	MGLL	NM_001388312.1		c.263-18345T>A		intron	N/A	NP_001375241.1
	MGLL	NM_001388313.1		c.233-18345T>A		intron	N/A	NP_001375242.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGLL	ENST00000265052.10	TSL:1 MANE Select	c.263-18345T>A		intron	N/A	ENSP00000265052.5	A0A0C4DFN3
	MGLL	ENST00000479967.5	TSL:1	n.355-18345T>A		intron	N/A
	MGLL	ENST00000959996.1		c.692-18345T>A		intron	N/A	ENSP00000630055.1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36274 AN: 152046 Hom.: 4550 Cov.: 33

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.239 AC: 36302 AN: 152164 Hom.: 4559 Cov.: 33 AF XY: 0.238 AC XY: 17682 AN XY: 74402

African (AFR) AF: 0.199 AC: 8279 AN: 41526

American (AMR) AF: 0.312 AC: 4779 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 724 AN: 3470

East Asian (EAS) AF: 0.137 AC: 709 AN: 5168

South Asian (SAS) AF: 0.153 AC: 737 AN: 4826

European-Finnish (FIN) AF: 0.244 AC: 2584 AN: 10590

Middle Eastern (MID) AF: 0.195 AC: 57 AN: 292

European-Non Finnish (NFE) AF: 0.262 AC: 17796 AN: 67970

Other (OTH) AF: 0.219 AC: 464 AN: 2114

Alfa AF: 0.121 Hom.: 216

Bravo AF: 0.240

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.19
PhyloP100		-3.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9759081; hg19: chr3-127459754;