Genetic Variant MGLL:c.400-136T>C (chr3-127721299-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007283.7(MGLL):c.400-136T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 686,400 control chromosomes in the GnomAD database, including 70,017 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 0.41 ( 13493 hom., cov: 32)

Exomes 𝑓: 0.45 ( 56524 hom. )

Consequence

MGLL
NM_007283.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.700

Publications

8 publications found

Variant links:

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]

MGLL links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007283.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MGLL	NM_007283.7	MANE Select	c.400-136T>C	intron	N/A	NP_009214.1	A0A0C4DFN3
MGLL	NM_001388312.1		c.400-136T>C	intron	N/A	NP_001375241.1
MGLL	NM_001388313.1		c.370-136T>C	intron	N/A	NP_001375242.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MGLL	ENST00000265052.10	TSL:1 MANE Select	c.400-136T>C	intron	N/A	ENSP00000265052.5	A0A0C4DFN3
MGLL	ENST00000398101.7	TSL:1	n.791-136T>C	intron	N/A
MGLL	ENST00000479967.5	TSL:1	n.492-136T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.411

AC:

62456

AN:

151994

Hom.:

13488

Cov.:

show subpopulations

Gnomad AFR

AF:

0.278

Gnomad AMI

AF:

0.261

Gnomad AMR

AF:

0.408

Gnomad ASJ

AF:

0.395

Gnomad EAS

AF:

0.531

Gnomad SAS

AF:

0.368

Gnomad FIN

AF:

0.480

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.480

Gnomad OTH

AF:

0.386

GnomAD4 exome

AF:

0.452

AC:

241232

AN:

534288

Hom.:

56524

AF XY:

0.446

AC XY:

126508

AN XY:

283906

show subpopulations

African (AFR)

AF:

0.262

AC:

3820

AN:

14588

American (AMR)

AF:

0.370

AC:

10109

AN:

27314

Ashkenazi Jewish (ASJ)

AF:

0.379

AC:

6963

AN:

18378

East Asian (EAS)

AF:

0.583

AC:

18367

AN:

31522

South Asian (SAS)

AF:

0.350

AC:

20300

AN:

58038

European-Finnish (FIN)

AF:

0.469

AC:

16100

AN:

34342

Middle Eastern (MID)

AF:

0.328

AC:

944

AN:

2874

European-Non Finnish (NFE)

AF:

0.478

AC:

152007

AN:

317886

Other (OTH)

AF:

0.430

AC:

12622

AN:

29346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

6063

12126

18189

24252

30315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1160

2320

3480

4640

5800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.411

AC:

62494

AN:

152112

Hom.:

13493

Cov.:

AF XY:

0.412

AC XY:

30602

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.278

AC:

11530

AN:

41492

American (AMR)

AF:

0.408

AC:

6242

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.395

AC:

1372

AN:

3470

East Asian (EAS)

AF:

0.531

AC:

2746

AN:

5176

South Asian (SAS)

AF:

0.367

AC:

1770

AN:

4818

European-Finnish (FIN)

AF:

0.480

AC:

5068

AN:

10564

Middle Eastern (MID)

AF:

0.313

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.480

AC:

32622

AN:

67982

Other (OTH)

AF:

0.386

AC:

814

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1860

3720

5581

7441

9301

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

594

1188

1782

2376

2970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.449

Hom.:

8538

Bravo

AF:

0.399

Asia WGS

AF:

0.411

AC:

1425

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

1.3

(source)

DANN

Benign

0.88

PhyloP100

-0.70

PromoterAI

0.029

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over