chr3-127761630-G-T

Variant names:

• chr3-127761630-G-T
• rs7652615
• NM_007283.7:c.262+20159C>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+20159C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.792 in 152,212 control chromosomes in the GnomAD database, including 48,145 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 0.79 (48145 hom., cov: 33)
• Consequence: MGLL NM_007283.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• 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]

ENSG00000302396 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGLL	NM_007283.7	c.262+20159C>A		intron_variant	Intron 3 of 7	ENST00000265052.10	NP_009214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGLL	ENST00000265052.10	c.262+20159C>A		intron_variant	Intron 3 of 7	1	NM_007283.7	ENSP00000265052.5

Frequencies

GnomAD3 genomes AF: 0.792 AC: 120408 AN: 152094 Hom.: 48115 Cov.: 33

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.865

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.872

Gnomad MID AF: 0.828

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.789

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

GnomAD4 genome AF: 0.792 AC: 120488 AN: 152212 Hom.: 48145 Cov.: 33 AF XY: 0.794 AC XY: 59090 AN XY: 74432

African (AFR) AF: 0.689 AC: 28624 AN: 41518

American (AMR) AF: 0.866 AC: 13245 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.801 AC: 2781 AN: 3472

East Asian (EAS) AF: 0.685 AC: 3547 AN: 5180

South Asian (SAS) AF: 0.737 AC: 3561 AN: 4830

European-Finnish (FIN) AF: 0.872 AC: 9230 AN: 10590

Middle Eastern (MID) AF: 0.829 AC: 242 AN: 292

European-Non Finnish (NFE) AF: 0.837 AC: 56890 AN: 68000

Other (OTH) AF: 0.787 AC: 1666 AN: 2116

Alfa AF: 0.825 Hom.: 64778

Bravo AF: 0.788

Asia WGS AF: 0.724 AC: 2518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.088
DANN	Benign	0.51
PhyloP100		-1.1
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: rs7652615; hg19: chr3-127480473; COSMIC: COSV54023628;