Genetic Variant LIPE:c.2968-46G>C (chr19-42402121-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005357.4(LIPE):c.2968-46G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.098 in 1,420,750 control chromosomes in the GnomAD database, including 7,656 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.082 ( 649 hom., cov: 31)

Exomes 𝑓: 0.10 ( 7007 hom. )

Consequence

LIPE
NM_005357.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0160

Publications

2 publications found

Variant links:

Genes affected

LIPE (HGNC:6621): (lipase E, hormone sensitive type) The protein encoded by this gene has a long and a short form, generated by use of alternative translational start codons. The long form is expressed in steroidogenic tissues such as testis, where it converts cholesteryl esters to free cholesterol for steroid hormone production. The short form is expressed in adipose tissue, among others, where it hydrolyzes stored triglycerides to free fatty acids. [provided by RefSeq, Jul 2008]

LIPE links:

LIPE-AS1 (HGNC:48589): (LIPE antisense RNA 1)

LIPE-AS1 links:

LOC101930071 (HGNC:):

LOC101930071 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 19-42402121-C-G is Benign according to our data. Variant chr19-42402121-C-G is described in ClinVar as Benign. ClinVar VariationId is 1234041.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005357.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
LIPE	NM_005357.4	MANE Select	c.2968-46G>C	intron	N/A	NP_005348.2
LIPE	NM_001416100.1		c.2218-46G>C	intron	N/A	NP_001403029.1
LIPE	NM_001416101.1		c.2203-46G>C	intron	N/A	NP_001403030.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LIPE	ENST00000244289.9	TSL:1 MANE Select	c.2968-46G>C	intron	N/A	ENSP00000244289.3	Q05469-1
LIPE-AS1	ENST00000594624.8	TSL:1	n.105+4897C>G	intron	N/A
LIPE	ENST00000599918.2	TSL:5	c.2992-46G>C	intron	N/A	ENSP00000472218.2	M0R201

Frequencies

GnomAD3 genomes

AF:

0.0825

AC:

12546

AN:

152074

Hom.:

653

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0319

Gnomad AMI

AF:

0.100

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.0914

Gnomad EAS

AF:

0.0407

Gnomad SAS

AF:

0.196

Gnomad FIN

AF:

0.0740

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.0986

Gnomad OTH

AF:

0.0934

GnomAD2 exomes

AF:

0.121

AC:

5185

AN:

42746

AF XY:

0.123

show subpopulations

Gnomad AFR exome

AF:

0.0346

Gnomad AMR exome

AF:

0.158

Gnomad ASJ exome

AF:

0.110

Gnomad EAS exome

AF:

0.0468

Gnomad FIN exome

AF:

0.0741

Gnomad NFE exome

AF:

0.128

Gnomad OTH exome

AF:

0.114

GnomAD4 exome

AF:

0.0998

AC:

126655

AN:

1268558

Hom.:

7007

Cov.:

AF XY:

0.102

AC XY:

62769

AN XY:

614198

show subpopulations

African (AFR)

AF:

0.0301

AC:

758

AN:

25152

American (AMR)

AF:

0.144

AC:

2730

AN:

18908

Ashkenazi Jewish (ASJ)

AF:

0.0899

AC:

1642

AN:

18256

East Asian (EAS)

AF:

0.0309

AC:

920

AN:

29772

South Asian (SAS)

AF:

0.187

AC:

11379

AN:

60978

European-Finnish (FIN)

AF:

0.0702

AC:

3004

AN:

42778

Middle Eastern (MID)

AF:

0.189

AC:

738

AN:

3896

European-Non Finnish (NFE)

AF:

0.0986

AC:

100181

AN:

1016384

Other (OTH)

AF:

0.101

AC:

5303

AN:

52434

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

6218

12436

18653

24871

31089

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3900

7800

11700

15600

19500

<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:

0.0823

AC:

12532

AN:

152192

Hom.:

649

Cov.:

AF XY:

0.0842

AC XY:

6263

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0318

AC:

1322

AN:

41542

American (AMR)

AF:

0.125

AC:

1907

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0914

AC:

317

AN:

3470

East Asian (EAS)

AF:

0.0406

AC:

210

AN:

5168

South Asian (SAS)

AF:

0.195

AC:

941

AN:

4828

European-Finnish (FIN)

AF:

0.0740

AC:

784

AN:

10600

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0986

AC:

6699

AN:

67970

Other (OTH)

AF:

0.0919

AC:

194

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

570

1141

1711

2282

2852

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

304

456

608

760

<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:

0.0907

Hom.:

Bravo

AF:

0.0835

Asia WGS

AF:

0.115

AC:

402

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.9

(source)

DANN

Benign

0.55

PhyloP100

0.016

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