rs7653663

Variant names:

• chr3-127756783-G-A
• rs7653663
• NM_007283.7:c.262+25006C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001388312.1(MGLL):​c.262+25006C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,110 control chromosomes in the GnomAD database, including 5,607 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 0.24 (5607 hom., cov: 32)
• Consequence: MGLL NM_001388312.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388312.1. 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+25006C>T		intron	N/A	NP_009214.1
	MGLL	NM_001388312.1		c.262+25006C>T		intron	N/A	NP_001375241.1
	MGLL	NM_001388313.1		c.232+25006C>T		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+25006C>T		intron	N/A	ENSP00000265052.5
	MGLL	ENST00000479967.5	TSL:1	n.354+25006C>T		intron	N/A
	MGLL	ENST00000959996.1		c.691+25006C>T		intron	N/A	ENSP00000630055.1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36801 AN: 151992 Hom.: 5583 Cov.: 32

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.242 AC: 36872 AN: 152110 Hom.: 5607 Cov.: 32 AF XY: 0.240 AC XY: 17848 AN XY: 74350

African (AFR) AF: 0.414 AC: 17150 AN: 41446

American (AMR) AF: 0.178 AC: 2716 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 542 AN: 3468

East Asian (EAS) AF: 0.419 AC: 2166 AN: 5168

South Asian (SAS) AF: 0.285 AC: 1374 AN: 4822

European-Finnish (FIN) AF: 0.110 AC: 1167 AN: 10600

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11075 AN: 68000

Other (OTH) AF: 0.250 AC: 527 AN: 2112

Alfa AF: 0.189 Hom.: 5798

Bravo AF: 0.254

Asia WGS AF: 0.331 AC: 1152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.38
PhyloP100		-0.14
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: rs7653663; hg19: chr3-127475626;