rs9852837

Positions:

• chr3-127772211-G-A
• chr3-127772211-G-T

Variant summary

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

The NM_007283.7(MGLL):​c.262+9578C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0356 in 152,118 control chromosomes in the GnomAD database, including 188 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 0.036 (188 hom., cov: 32)
• Consequence: MGLL NM_007283.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGLL	NM_007283.7	c.262+9578C>T		intron_variant		ENST00000265052.10	NP_009214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGLL	ENST00000265052.10	c.262+9578C>T		intron_variant		1	NM_007283.7	ENSP00000265052

Frequencies

GnomAD3 genomes AF: 0.0357 AC: 5425 AN: 152000 Hom.: 189 Cov.: 32

Gnomad AFR AF: 0.0213

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0191

Gnomad ASJ AF: 0.0214

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.0224

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0353

Gnomad OTH AF: 0.0302

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

GnomAD4 genome AF: 0.0356 AC: 5419 AN: 152118 Hom.: 188 Cov.: 32 AF XY: 0.0375 AC XY: 2792 AN XY: 74362

Gnomad4 AFR AF: 0.0213

Gnomad4 AMR AF: 0.0190

Gnomad4 ASJ AF: 0.0214

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.0224

Gnomad4 NFE AF: 0.0353

Gnomad4 OTH AF: 0.0308

Alfa AF: 0.0307 Hom.: 82

Bravo AF: 0.0318

Asia WGS AF: 0.127 AC: 440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.36
DANN	Benign	0.49

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: rs9852837; hg19: chr3-127491054;