3-127697299-C-T

Variant names:

• chr3-127697299-C-T
• rs782440
• NM_007283.7:c.601-2109G>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.601-2109G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 152,220 control chromosomes in the GnomAD database, including 25,836 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 0.55 (25836 hom., cov: 34)
• Consequence: MGLL NM_007283.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.41
• Publications: 7 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGLL	NM_007283.7	c.601-2109G>A		intron_variant	Intron 6 of 7	ENST00000265052.10	NP_009214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGLL	ENST00000265052.10	c.601-2109G>A		intron_variant	Intron 6 of 7	1	NM_007283.7	ENSP00000265052.5

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83706 AN: 152102 Hom.: 25793 Cov.: 34

Gnomad AFR AF: 0.845

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.550 AC: 83797 AN: 152220 Hom.: 25836 Cov.: 34 AF XY: 0.546 AC XY: 40633 AN XY: 74416

African (AFR) AF: 0.845 AC: 35113 AN: 41552

American (AMR) AF: 0.449 AC: 6874 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1647 AN: 3472

East Asian (EAS) AF: 0.600 AC: 3097 AN: 5160

South Asian (SAS) AF: 0.526 AC: 2543 AN: 4832

European-Finnish (FIN) AF: 0.382 AC: 4043 AN: 10592

Middle Eastern (MID) AF: 0.644 AC: 188 AN: 292

European-Non Finnish (NFE) AF: 0.421 AC: 28617 AN: 68000

Other (OTH) AF: 0.553 AC: 1166 AN: 2110

Alfa AF: 0.480 Hom.: 28629

Bravo AF: 0.568

Asia WGS AF: 0.585 AC: 2036 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.14
DANN	Benign	0.56
PhyloP100		-2.4
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: rs782440; hg19: chr3-127416142;