3-127775021-C-T

Variant names:

• chr3-127775021-C-T
• rs567384
• NM_007283.7:c.262+6768G>A

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+6768G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 152,108 control chromosomes in the GnomAD database, including 56,737 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 0.86 (56737 hom., cov: 31)
• Consequence: MGLL NM_007283.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.888 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+6768G>A		intron	N/A	NP_009214.1	A0A0C4DFN3
	MGLL	NM_001388312.1		c.262+6768G>A		intron	N/A	NP_001375241.1
	MGLL	NM_001388313.1		c.232+6768G>A		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+6768G>A		intron	N/A	ENSP00000265052.5	A0A0C4DFN3
	MGLL	ENST00000479967.5	TSL:1	n.354+6768G>A		intron	N/A
	MGLL	ENST00000959996.1		c.691+6768G>A		intron	N/A	ENSP00000630055.1

Frequencies

GnomAD3 genomes AF: 0.861 AC: 130834 AN: 151990 Hom.: 56688 Cov.: 31

Gnomad AFR AF: 0.896

Gnomad AMI AF: 0.938

Gnomad AMR AF: 0.803

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.862

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.878

Gnomad OTH AF: 0.877

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

GnomAD4 genome AF: 0.861 AC: 130938 AN: 152108 Hom.: 56737 Cov.: 31 AF XY: 0.855 AC XY: 63575 AN XY: 74356

African (AFR) AF: 0.896 AC: 37154 AN: 41464

American (AMR) AF: 0.803 AC: 12260 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.916 AC: 3182 AN: 3472

East Asian (EAS) AF: 0.546 AC: 2820 AN: 5168

South Asian (SAS) AF: 0.770 AC: 3715 AN: 4826

European-Finnish (FIN) AF: 0.862 AC: 9118 AN: 10578

Middle Eastern (MID) AF: 0.952 AC: 280 AN: 294

European-Non Finnish (NFE) AF: 0.878 AC: 59698 AN: 68004

Other (OTH) AF: 0.878 AC: 1856 AN: 2114

Alfa AF: 0.869 Hom.: 202392

Bravo AF: 0.859

Asia WGS AF: 0.723 AC: 2512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.90
DANN	Benign	0.28
PhyloP100		0.013
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: rs567384; hg19: chr3-127493864;