3-127784460-C-T

Variant names:

• chr3-127784460-C-T
• rs17203666
• NM_007283.7:c.156-2565G>A

Variant summary

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

The NM_007283.7(MGLL):​c.156-2565G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,132 control chromosomes in the GnomAD database, including 1,932 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 0.14 (1932 hom., cov: 32)
• Consequence: MGLL NM_007283.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 3 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGLL	NM_007283.7	c.156-2565G>A		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.156-2565G>A		intron_variant	Intron 2 of 7	1	NM_007283.7	ENSP00000265052.5

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21552 AN: 152014 Hom.: 1925 Cov.: 32

Gnomad AFR AF: 0.0378

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.142 AC: 21561 AN: 152132 Hom.: 1932 Cov.: 32 AF XY: 0.145 AC XY: 10789 AN XY: 74364

African (AFR) AF: 0.0377 AC: 1564 AN: 41524

American (AMR) AF: 0.151 AC: 2303 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 587 AN: 3470

East Asian (EAS) AF: 0.261 AC: 1347 AN: 5170

South Asian (SAS) AF: 0.200 AC: 965 AN: 4818

European-Finnish (FIN) AF: 0.220 AC: 2328 AN: 10574

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11968 AN: 67972

Other (OTH) AF: 0.153 AC: 324 AN: 2112

Alfa AF: 0.130 Hom.: 637

Bravo AF: 0.131

Asia WGS AF: 0.234 AC: 813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.26
DANN	Benign	0.48
PhyloP100		-1.1
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: rs17203666; hg19: chr3-127503303;