3-127721299-A-G

Position:

• chr3-127721299-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007283.7(MGLL):​c.400-136T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 686,400 control chromosomes in the GnomAD database, including 70,017 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 0.41 (13493 hom., cov: 32)
  • Exomes 𝑓: 0.45 (56524 hom.)
• Consequence: MGLL NM_007283.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.700

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=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MGLL	NM_007283.7	c.400-136T>C		intron_variant		ENST00000265052.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MGLL	ENST00000265052.10	c.400-136T>C		intron_variant		1	NM_007283.7

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62456 AN: 151994 Hom.: 13488 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.386

GnomAD4 exome AF: 0.452 AC: 241232 AN: 534288 Hom.: 56524 AF XY: 0.446 AC XY: 126508 AN XY: 283906

Gnomad4 AFR exome AF: 0.262

Gnomad4 AMR exome AF: 0.370

Gnomad4 ASJ exome AF: 0.379

Gnomad4 EAS exome AF: 0.583

Gnomad4 SAS exome AF: 0.350

Gnomad4 FIN exome AF: 0.469

Gnomad4 NFE exome AF: 0.478

Gnomad4 OTH exome AF: 0.430

GnomAD4 genome AF: 0.411 AC: 62494 AN: 152112 Hom.: 13493 Cov.: 32 AF XY: 0.412 AC XY: 30602 AN XY: 74348

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.531

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.480

Gnomad4 OTH AF: 0.386

Alfa AF: 0.448 Hom.: 7584

Bravo AF: 0.399

Asia WGS AF: 0.411 AC: 1425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.3
DANN	Benign	0.88

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: rs555183; hg19: chr3-127440142; COSMIC: COSV54026854; COSMIC: COSV54026854;