rs520154

Variant names:

• chr3-127764154-G-A
• rs520154
• NM_007283.7:c.262+17635C>T

Variant summary

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

The NM_007283.7(MGLL):​c.262+17635C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0603 in 152,240 control chromosomes in the GnomAD database, including 461 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 0.060 (461 hom., cov: 32)
• Consequence: MGLL NM_007283.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.21 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.262+17635C>T		intron	N/A	NP_009214.1	A0A0C4DFN3
	MGLL	NM_001388312.1		c.262+17635C>T		intron	N/A	NP_001375241.1
	MGLL	NM_001388313.1		c.232+17635C>T		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.262+17635C>T		intron	N/A	ENSP00000265052.5	A0A0C4DFN3
	MGLL	ENST00000479967.5	TSL:1	n.354+17635C>T		intron	N/A
	MGLL	ENST00000959996.1		c.691+17635C>T		intron	N/A	ENSP00000630055.1

Frequencies

GnomAD3 genomes AF: 0.0603 AC: 9169 AN: 152122 Hom.: 461 Cov.: 32

Gnomad AFR AF: 0.0967

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0324

Gnomad ASJ AF: 0.0294

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.0216

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0331

Gnomad OTH AF: 0.0525

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

GnomAD4 genome AF: 0.0603 AC: 9176 AN: 152240 Hom.: 461 Cov.: 32 AF XY: 0.0617 AC XY: 4595 AN XY: 74430

African (AFR) AF: 0.0969 AC: 4023 AN: 41524

American (AMR) AF: 0.0324 AC: 495 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0294 AC: 102 AN: 3472

East Asian (EAS) AF: 0.220 AC: 1142 AN: 5180

South Asian (SAS) AF: 0.165 AC: 798 AN: 4828

European-Finnish (FIN) AF: 0.0216 AC: 229 AN: 10592

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0331 AC: 2250 AN: 68022

Other (OTH) AF: 0.0534 AC: 113 AN: 2116

Alfa AF: 0.0536 Hom.: 67

Bravo AF: 0.0614

Asia WGS AF: 0.179 AC: 623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.51
PhyloP100		0.053
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs520154;

hg19: chr3-127482997;