Genetic Variant NM_005357.4:c.883+2898A>G (chr19-42423369-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_005357.4(LIPE):c.883+2898A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0764 in 1,259,560 control chromosomes in the GnomAD database, including 5,520 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 0.12 ( 1611 hom., cov: 32)

Exomes 𝑓: 0.070 ( 3909 hom. )

Consequence

LIPE
NM_005357.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.719

Publications

9 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:

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=-0.73).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPE	NM_005357.4 link	c.883+2898A>G		intron_variant	Intron 1 of 9	ENST00000244289.9	NP_005348.2	Q05469-1A8K8W7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPE	ENST00000244289.9 link	c.883+2898A>G		intron_variant	Intron 1 of 9	1	NM_005357.4	ENSP00000244289.3		Q05469-1

Frequencies

GnomAD3 genomes

AF:

0.121

AC:

18364

AN:

152076

Hom.:

1595

Cov.:

show subpopulations

Gnomad AFR

AF:

0.247

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.127

Gnomad ASJ

AF:

0.0838

Gnomad EAS

AF:

0.0825

Gnomad SAS

AF:

0.148

Gnomad FIN

AF:

0.0461

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.0583

Gnomad OTH

AF:

0.115

GnomAD2 exomes

AF:

0.106

AC:

14135

AN:

133740

AF XY:

0.104

show subpopulations

Gnomad AFR exome

AF:

0.257

Gnomad AMR exome

AF:

0.152

Gnomad ASJ exome

AF:

0.0809

Gnomad EAS exome

AF:

0.100

Gnomad FIN exome

AF:

0.0405

Gnomad NFE exome

AF:

0.0591

Gnomad OTH exome

AF:

0.0984

GnomAD4 exome

AF:

0.0703

AC:

77821

AN:

1107366

Hom.:

3909

Cov.:

AF XY:

0.0726

AC XY:

39537

AN XY:

544832

show subpopulations

African (AFR)

AF:

0.267

AC:

6340

AN:

23748

American (AMR)

AF:

0.152

AC:

4293

AN:

28152

Ashkenazi Jewish (ASJ)

AF:

0.0803

AC:

1264

AN:

15736

East Asian (EAS)

AF:

0.0959

AC:

1211

AN:

12630

South Asian (SAS)

AF:

0.144

AC:

10913

AN:

75614

European-Finnish (FIN)

AF:

0.0419

AC:

546

AN:

13016

Middle Eastern (MID)

AF:

0.232

AC:

1003

AN:

4324

European-Non Finnish (NFE)

AF:

0.0544

AC:

48636

AN:

893680

Other (OTH)

AF:

0.0893

AC:

3615

AN:

40466

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

3539

7078

10617

14156

17695

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2302

4604

6906

9208

11510

<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:

0.121

AC:

18423

AN:

152194

Hom.:

1611

Cov.:

AF XY:

0.122

AC XY:

9043

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.248

AC:

10278

AN:

41508

American (AMR)

AF:

0.127

AC:

1945

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0838

AC:

291

AN:

3472

East Asian (EAS)

AF:

0.0823

AC:

425

AN:

5162

South Asian (SAS)

AF:

0.147

AC:

709

AN:

4822

European-Finnish (FIN)

AF:

0.0461

AC:

489

AN:

10614

Middle Eastern (MID)

AF:

0.204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0583

AC:

3966

AN:

67994

Other (OTH)

AF:

0.117

AC:

246

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

797

1595

2392

3190

3987

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

200

400

600

800

1000

<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:

0.0808

Hom.:

311

Bravo

AF:

0.134

Asia WGS

AF:

0.144

AC:

501

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

9.3

(source)

DANN

Benign

0.74

PhyloP100

-0.72

PromoterAI

0.15

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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