19-42402058-G-A

Variant names:

• chr19-42402058-G-A
• rs370837760
• NM_005357.4:c.2985C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_005357.4(LIPE):​c.2985C>T​(p.Pro995Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000885 in 1,504,350 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00090 (1 hom.)
• Consequence: LIPE NM_005357.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.22

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

LOC101930071 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 19-42402058-G-A is Benign according to our data. Variant chr19-42402058-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 435763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.22 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPE	NM_005357.4	c.2985C>T	p.Pro995Pro	synonymous_variant	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	c.2985C>T	p.Pro995Pro	synonymous_variant	Exon 10 of 10	1	NM_005357.4	ENSP00000244289.3

Frequencies

GnomAD3 genomes AF: 0.000716 AC: 109 AN: 152260 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000852

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000734 AC: 79 AN: 107668 AF XY: 0.000808

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000902

Gnomad ASJ exome AF: 0.000388

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000759

Gnomad NFE exome AF: 0.00113

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000905 AC: 1223 AN: 1351972 Hom.: 1 Cov.: 36 AF XY: 0.000929 AC XY: 615 AN XY: 662110

Gnomad4 AFR exome AF: 0.000139 AC: 4 AN: 28802

Gnomad4 AMR exome AF: 0.000914 AC: 29 AN: 31734

Gnomad4 ASJ exome AF: 0.000356 AC: 8 AN: 22474

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 33408

Gnomad4 SAS exome AF: 0.000801 AC: 58 AN: 72374

Gnomad4 FIN exome AF: 0.000129 AC: 6 AN: 46374

Gnomad4 NFE exome AF: 0.00103 AC: 1093 AN: 1056406

Gnomad4 Remaining exome AF: 0.000447 AC: 25 AN: 55922

GnomAD4 genome AF: 0.000715 AC: 109 AN: 152378 Hom.: 0 Cov.: 32 AF XY: 0.000752 AC XY: 56 AN XY: 74512

Gnomad4 AFR AF: 0.000264 AC: 0.000264461 AN: 0.000264461

Gnomad4 AMR AF: 0.00229 AC: 0.00228639 AN: 0.00228639

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000828 AC: 0.000827815 AN: 0.000827815

Gnomad4 FIN AF: 0.0000941 AC: 0.0000940557 AN: 0.0000940557

Gnomad4 NFE AF: 0.000853 AC: 0.000852515 AN: 0.000852515

Gnomad4 OTH AF: 0.00 AC: 0 AN: 0

Alfa AF: 0.000587 Hom.: 0

Bravo AF: 0.000740

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

LIPE: BP4, BP7 -

not specified Benign:1

Jun 02, 2016

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

LIPE-related disorder Benign:1

Aug 26, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	13
DANN	Uncertain	0.98
Mutation Taster		=100/0	polymorphism

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

LitVar

Other links and lift over

dbSNP: rs370837760; hg19: chr19-42906210;