dbSNP rs555183: 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:

Genome browser will be placed here

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGLL	NM_007283.7 link	c.400-136T>C		intron_variant	Intron 4 of 7	ENST00000265052.10	NP_009214.1	Q99685A0A0C4DFN3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGLL	ENST00000265052.10 link	c.400-136T>C		intron_variant	Intron 4 of 7	1	NM_007283.7	ENSP00000265052.5		A0A0C4DFN3

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over