3-127697299-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MGLL	NM_007283.7	c.601-2109G>A		intron_variant		ENST00000265052.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MGLL	ENST00000265052.10	c.601-2109G>A		intron_variant		1	NM_007283.7

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

Gnomad4 AFR AF: 0.845

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.474

Gnomad4 EAS AF: 0.600

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.553

Alfa AF: 0.485 Hom.: 3352

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs782440; hg19: chr3-127416142;