chr3-127808323-A-G

Variant names:

• chr3-127808323-A-G
• rs9289319
• NM_007283.7:c.155+13371T>C

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+13371T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 152,108 control chromosomes in the GnomAD database, including 7,515 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 0.28 (7515 hom., cov: 32)
• Consequence: MGLL NM_007283.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.567
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGLL	NM_007283.7	c.155+13371T>C		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+13371T>C		intron_variant	Intron 2 of 7	1	NM_007283.7	ENSP00000265052.5

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43042 AN: 151990 Hom.: 7487 Cov.: 32

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.284 AC: 43127 AN: 152108 Hom.: 7515 Cov.: 32 AF XY: 0.281 AC XY: 20906 AN XY: 74370

African (AFR) AF: 0.491 AC: 20354 AN: 41456

American (AMR) AF: 0.255 AC: 3895 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 741 AN: 3468

East Asian (EAS) AF: 0.246 AC: 1270 AN: 5160

South Asian (SAS) AF: 0.297 AC: 1435 AN: 4826

European-Finnish (FIN) AF: 0.120 AC: 1273 AN: 10592

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13341 AN: 67986

Other (OTH) AF: 0.237 AC: 501 AN: 2112

Alfa AF: 0.228 Hom.: 1683

Bravo AF: 0.299

Asia WGS AF: 0.275 AC: 956 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.66
PhyloP100		-0.57
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: rs9289319; hg19: chr3-127527166;