3-127697630-C-T

Variant names:

• chr3-127697630-C-T
• rs6765071
• NM_007283.7:c.601-2440G>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.601-2440G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,156 control chromosomes in the GnomAD database, including 1,907 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 0.15 (1907 hom., cov: 33)
• Consequence: MGLL NM_007283.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200
• Publications: 3 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.185 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.601-2440G>A		intron	N/A	NP_009214.1
	MGLL	NM_001388312.1		c.679-2440G>A		intron	N/A	NP_001375241.1
	MGLL	NM_001388313.1		c.649-2440G>A		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.601-2440G>A		intron	N/A	ENSP00000265052.5
	MGLL	ENST00000398101.7	TSL:1	n.992-2440G>A		intron	N/A
	MGLL	ENST00000476682.1	TSL:1	n.3572-2440G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23279 AN: 152036 Hom.: 1907 Cov.: 33

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.153 AC: 23288 AN: 152156 Hom.: 1907 Cov.: 33 AF XY: 0.154 AC XY: 11455 AN XY: 74382

African (AFR) AF: 0.118 AC: 4912 AN: 41506

American (AMR) AF: 0.191 AC: 2923 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 631 AN: 3470

East Asian (EAS) AF: 0.122 AC: 634 AN: 5178

South Asian (SAS) AF: 0.168 AC: 808 AN: 4820

European-Finnish (FIN) AF: 0.158 AC: 1676 AN: 10602

Middle Eastern (MID) AF: 0.360 AC: 105 AN: 292

European-Non Finnish (NFE) AF: 0.162 AC: 10989 AN: 67978

Other (OTH) AF: 0.201 AC: 426 AN: 2116

Alfa AF: 0.157 Hom.: 5058

Bravo AF: 0.156

Asia WGS AF: 0.158 AC: 552 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.9
DANN	Benign	0.67
PhyloP100		0.0020
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: rs6765071; hg19: chr3-127416473; COSMIC: COSV54023577;