3-127754645-A-G

Variant names:

• chr3-127754645-A-G
• rs6778770
• NM_007283.7:c.262+27144T>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.262+27144T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,218 control chromosomes in the GnomAD database, including 3,263 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 0.19 (3263 hom., cov: 33)
• Consequence: MGLL NM_007283.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.97
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.243 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGLL	NM_007283.7	MANE Select	c.262+27144T>C		intron	N/A	NP_009214.1
	MGLL	NM_001388312.1		c.262+27144T>C		intron	N/A	NP_001375241.1
	MGLL	NM_001388313.1		c.232+27144T>C		intron	N/A	NP_001375242.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGLL	ENST00000265052.10	TSL:1 MANE Select	c.262+27144T>C		intron	N/A	ENSP00000265052.5
	MGLL	ENST00000479967.5	TSL:1	n.354+27144T>C		intron	N/A
	MGLL	ENST00000398104.6	TSL:5	c.232+27144T>C		intron	N/A	ENSP00000381176.1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28891 AN: 152100 Hom.: 3268 Cov.: 33

Gnomad AFR AF: 0.0838

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.190 AC: 28880 AN: 152218 Hom.: 3263 Cov.: 33 AF XY: 0.187 AC XY: 13886 AN XY: 74418

African (AFR) AF: 0.0837 AC: 3477 AN: 41550

American (AMR) AF: 0.177 AC: 2702 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1076 AN: 3470

East Asian (EAS) AF: 0.228 AC: 1182 AN: 5174

South Asian (SAS) AF: 0.222 AC: 1072 AN: 4822

European-Finnish (FIN) AF: 0.174 AC: 1846 AN: 10602

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.246 AC: 16752 AN: 67982

Other (OTH) AF: 0.215 AC: 454 AN: 2114

Alfa AF: 0.218 Hom.: 4221

Bravo AF: 0.186

Asia WGS AF: 0.215 AC: 747 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.75
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs6778770; hg19: chr3-127473488;