rs35948688

Positions:

• chr3-127813405-T-C

Variant summary

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

The NM_007283.7(MGLL):​c.155+8289A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,214 control chromosomes in the GnomAD database, including 1,449 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 0.12 (1449 hom., cov: 32)
• Consequence: MGLL NM_007283.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MGLL	NM_007283.7	c.155+8289A>G		intron_variant		ENST00000265052.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MGLL	ENST00000265052.10	c.155+8289A>G		intron_variant		1	NM_007283.7

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18261 AN: 152096 Hom.: 1449 Cov.: 32

Gnomad AFR AF: 0.0307

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0394

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.0939

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.120 AC: 18260 AN: 152214 Hom.: 1449 Cov.: 32 AF XY: 0.120 AC XY: 8932 AN XY: 74418

Gnomad4 AFR AF: 0.0306

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.0395

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.0939

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.111

Alfa AF: 0.139 Hom.: 225

Bravo AF: 0.117

Asia WGS AF: 0.106 AC: 367 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	0.038
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: rs35948688; hg19: chr3-127532248;