3-127809413-C-G

Variant names:

• chr3-127809413-C-G
• rs9289320
• NM_007283.7:c.155+12281G>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+12281G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 151,838 control chromosomes in the GnomAD database, including 6,099 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 0.26 (6099 hom., cov: 31)
• Consequence: MGLL NM_007283.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.986
• Publications: 1 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.417 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.155+12281G>C		intron	N/A	NP_009214.1	A0A0C4DFN3
	MGLL	NM_001388312.1		c.155+12281G>C		intron	N/A	NP_001375241.1
	MGLL	NM_001388313.1		c.125+12281G>C		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.155+12281G>C		intron	N/A	ENSP00000265052.5	A0A0C4DFN3
	MGLL	ENST00000479967.5	TSL:1	n.247+12281G>C		intron	N/A
	MGLL	ENST00000959996.1		c.156-10483G>C		intron	N/A	ENSP00000630055.1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39718 AN: 151720 Hom.: 6081 Cov.: 31

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.262 AC: 39785 AN: 151838 Hom.: 6099 Cov.: 31 AF XY: 0.260 AC XY: 19259 AN XY: 74212

African (AFR) AF: 0.422 AC: 17446 AN: 41356

American (AMR) AF: 0.248 AC: 3783 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 741 AN: 3470

East Asian (EAS) AF: 0.234 AC: 1209 AN: 5156

South Asian (SAS) AF: 0.251 AC: 1210 AN: 4812

European-Finnish (FIN) AF: 0.120 AC: 1270 AN: 10554

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.196 AC: 13338 AN: 67910

Other (OTH) AF: 0.224 AC: 474 AN: 2112

Alfa AF: 0.0981 Hom.: 126

Bravo AF: 0.276

Asia WGS AF: 0.240 AC: 835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.59
DANN	Benign	0.18
PhyloP100		-0.99
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: rs9289320; hg19: chr3-127528256;