rs549662

Variant names:

• chr3-127763193-G-A
• rs549662
• NM_007283.7:c.262+18596C>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+18596C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 151,900 control chromosomes in the GnomAD database, including 48,718 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 0.80 (48718 hom., cov: 33)
• Consequence: MGLL NM_007283.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.389
• Publications: 8 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGLL	NM_007283.7	c.262+18596C>T		intron_variant	Intron 3 of 7	ENST00000265052.10	NP_009214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGLL	ENST00000265052.10	c.262+18596C>T		intron_variant	Intron 3 of 7	1	NM_007283.7	ENSP00000265052.5

Frequencies

GnomAD3 genomes AF: 0.799 AC: 121214 AN: 151786 Hom.: 48686 Cov.: 33

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.804

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.789

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

GnomAD4 genome AF: 0.799 AC: 121304 AN: 151900 Hom.: 48718 Cov.: 33 AF XY: 0.799 AC XY: 59290 AN XY: 74244

African (AFR) AF: 0.764 AC: 31694 AN: 41488

American (AMR) AF: 0.824 AC: 12534 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.804 AC: 2790 AN: 3468

East Asian (EAS) AF: 0.524 AC: 2622 AN: 5000

South Asian (SAS) AF: 0.719 AC: 3446 AN: 4794

European-Finnish (FIN) AF: 0.866 AC: 9193 AN: 10612

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.830 AC: 56429 AN: 68008

Other (OTH) AF: 0.788 AC: 1668 AN: 2116

Alfa AF: 0.816 Hom.: 25982

Bravo AF: 0.791

Asia WGS AF: 0.666 AC: 2302 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.1
DANN	Benign	0.76
PhyloP100		0.39
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: rs549662; hg19: chr3-127482036; COSMIC: COSV54023638;