chr3-127755187-G-A

Variant names:

• chr3-127755187-G-A
• rs664910
• NM_007283.7:c.262+26602C>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.262+26602C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 152,048 control chromosomes in the GnomAD database, including 31,810 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 0.63 (31810 hom., cov: 32)
• Consequence: MGLL NM_007283.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135
• Publications: 27 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=-0.7).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGLL	NM_007283.7	c.262+26602C>T		intron_variant	Intron 3 of 7	ENST00000265052.10	NP_009214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGLL	ENST00000265052.10	c.262+26602C>T		intron_variant	Intron 3 of 7	1	NM_007283.7	ENSP00000265052.5

Frequencies

GnomAD3 genomes AF: 0.632 AC: 96055 AN: 151930 Hom.: 31795 Cov.: 32

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.710

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.632 AC: 96092 AN: 152048 Hom.: 31810 Cov.: 32 AF XY: 0.636 AC XY: 47239 AN XY: 74316

African (AFR) AF: 0.478 AC: 19799 AN: 41462

American (AMR) AF: 0.740 AC: 11304 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 2641 AN: 3470

East Asian (EAS) AF: 0.269 AC: 1388 AN: 5162

South Asian (SAS) AF: 0.621 AC: 2989 AN: 4814

European-Finnish (FIN) AF: 0.780 AC: 8249 AN: 10574

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.699 AC: 47536 AN: 67974

Other (OTH) AF: 0.623 AC: 1315 AN: 2110

Alfa AF: 0.673 Hom.: 121001

Bravo AF: 0.620

Asia WGS AF: 0.451 AC: 1566 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.4
DANN	Benign	0.90
PhyloP100		-0.14
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: rs664910; hg19: chr3-127474030;