chr3-127811944-G-A

Variant names:

• chr3-127811944-G-A
• rs28753886
• NM_007283.7:c.155+9750C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007283.7(MGLL):​c.155+9750C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,246 control chromosomes in the GnomAD database, including 1,554 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 (1554 hom., cov: 33)
• Consequence: MGLL NM_007283.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.360
• Publications: 1 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGLL	NM_007283.7	c.155+9750C>T		intron_variant	Intron 2 of 7	ENST00000265052.10	NP_009214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGLL	ENST00000265052.10	c.155+9750C>T		intron_variant	Intron 2 of 7	1	NM_007283.7	ENSP00000265052.5

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19006 AN: 152128 Hom.: 1554 Cov.: 33

Gnomad AFR AF: 0.0321

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.0398

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.125 AC: 19006 AN: 152246 Hom.: 1554 Cov.: 33 AF XY: 0.125 AC XY: 9281 AN XY: 74454

African (AFR) AF: 0.0320 AC: 1330 AN: 41572

American (AMR) AF: 0.168 AC: 2569 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 566 AN: 3464

East Asian (EAS) AF: 0.0399 AC: 207 AN: 5188

South Asian (SAS) AF: 0.167 AC: 807 AN: 4832

European-Finnish (FIN) AF: 0.103 AC: 1088 AN: 10602

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11913 AN: 67986

Other (OTH) AF: 0.115 AC: 244 AN: 2114

Alfa AF: 0.120 Hom.: 457

Bravo AF: 0.122

Asia WGS AF: 0.103 AC: 357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.6
DANN	Benign	0.94
PhyloP100		-0.36
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: rs28753886; hg19: chr3-127530787;