Genetic Variant LIPE:p.Gly1074_Arg1075insArgArgGlyLeuArgGlyTerThrGlyAlaAlaGlyValAspGlyGlyCysGlyGly (chr19-42401821-C-CCCCCCGCAGCCCCCGTCTACCCCCGCAGCCCCCGTCTACCCCCGCAGCCCCCGTCTA) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PVS1_Moderate

The NM_005357.4(LIPE):c.3221_3222insTAGACGGGGGCTGCGGGGGTAGACGGGGGCTGCGGGGGTAGACGGGGGCTGCGGGGG(p.Gly1074_Arg1075insArgArgGlyLeuArgGlyTerThrGlyAlaAlaGlyValAspGlyGlyCysGlyGly) variant causes a stop gained, disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000753 in 1,328,364 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

LIPE
NM_005357.4 stop_gained, disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.38

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0031 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPE	NM_005357.4 link	c.3221_3222insTAGACGGGGGCTGCGGGGGTAGACGGGGGCTGCGGGGGTAGACGGGGGCTGCGGGGG	p.Gly1074_Arg1075insArgArgGlyLeuArgGlyTerThrGlyAlaAlaGlyValAspGlyGlyCysGlyGly	stop_gained, disruptive_inframe_insertion	Exon 10 of 10	ENST00000244289.9	NP_005348.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPE	ENST00000244289.9 link	c.3221_3222insTAGACGGGGGCTGCGGGGGTAGACGGGGGCTGCGGGGGTAGACGGGGGCTGCGGGGG	p.Gly1074_Arg1075insArgArgGlyLeuArgGlyTerThrGlyAlaAlaGlyValAspGlyGlyCysGlyGly	stop_gained, disruptive_inframe_insertion	Exon 10 of 10	1	NM_005357.4	ENSP00000244289.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.53e-7

AC:

AN:

1328364

Hom.:

Cov.:

AF XY:

0.00000153

AC XY:

AN XY:

652630

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27848

American (AMR)

AF:

0.00

AC:

AN:

26492

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21122

East Asian (EAS)

AF:

0.00

AC:

AN:

33480

South Asian (SAS)

AF:

0.00

AC:

AN:

69932

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40310

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3806

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1050220

Other (OTH)

AF:

0.0000181

AC:

AN:

55154

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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19-42401821-CCCCCCGCAGCCCCCGTCTA-CCCCCCGCAGCCCCCGTCTACCCCCGCAGCCCCCGTCTACCCCCGCAGCCCCCGTCTACCCCCGCAGCCCCCGTCTA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over