rs874546

Variant names:

• chr3-127819569-A-G
• rs874546
• NM_007283.7:c.155+2125T>C

Variant summary

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

The NM_007283.7(MGLL):​c.155+2125T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 151,788 control chromosomes in the GnomAD database, including 10,189 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 0.31 (10189 hom., cov: 31)
• Consequence: MGLL NM_007283.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 7 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGLL	NM_007283.7	c.155+2125T>C		intron_variant	Intron 2 of 7	ENST00000265052.10	NP_009214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGLL	ENST00000265052.10	c.155+2125T>C		intron_variant	Intron 2 of 7	1	NM_007283.7	ENSP00000265052.5

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46661 AN: 151672 Hom.: 10149 Cov.: 31

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.0988

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.308 AC: 46754 AN: 151788 Hom.: 10189 Cov.: 31 AF XY: 0.305 AC XY: 22611 AN XY: 74190

African (AFR) AF: 0.618 AC: 25560 AN: 41358

American (AMR) AF: 0.269 AC: 4105 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 714 AN: 3468

East Asian (EAS) AF: 0.245 AC: 1267 AN: 5164

South Asian (SAS) AF: 0.311 AC: 1492 AN: 4802

European-Finnish (FIN) AF: 0.0988 AC: 1043 AN: 10554

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11702 AN: 67902

Other (OTH) AF: 0.260 AC: 547 AN: 2104

Alfa AF: 0.213 Hom.: 18899

Bravo AF: 0.329

Asia WGS AF: 0.305 AC: 1059 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.40
DANN	Benign	0.83
PhyloP100		-1.1
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: rs874546; hg19: chr3-127538412;