Variant 19-42426852-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005357.4(LIPE):c.298T>C(p.Tyr100His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 1,614,018 control chromosomes in the GnomAD database, including 2,066 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.066 ( 1047 hom., cov: 31)

Exomes 𝑓: 0.0078 ( 1019 hom. )

Consequence

LIPE
NM_005357.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.208

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014833629).

BP6

Variant 19-42426852-A-G is Benign according to our data. Variant chr19-42426852-A-G is described in ClinVar as [Benign]. Clinvar id is 1243216.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LIPE	NM_005357.4 linkuse as main transcript	c.298T>C	p.Tyr100His	missense_variant	1/10	ENST00000244289.9
LIPE-AS1	NR_073180.1 linkuse as main transcript	n.77+29628A>G		intron_variant, non_coding_transcript_variant
LIPE	XM_005258937.4 linkuse as main transcript	c.298T>C	p.Tyr100His	missense_variant	1/9
LIPE-AS1	NR_073179.1 linkuse as main transcript	n.1450+1648A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPE	ENST00000244289.9 linkuse as main transcript	c.298T>C	p.Tyr100His	missense_variant	1/10	1	NM_005357.4	P1	Q05469-1
LIPE-AS1	ENST00000594624.7 linkuse as main transcript	n.66+29628A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0656

AC:

9977

AN:

152006

Hom.:

1037

Cov.:

show subpopulations

Gnomad AFR

AF:

0.224

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0305

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00150

Gnomad OTH

AF:

0.0533

GnomAD3 exomes

AF:

0.0185

AC:

4643

AN:

251452

Hom.:

477

AF XY:

0.0135

AC XY:

1828

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.234

Gnomad AMR exome

AF:

0.0134

Gnomad ASJ exome

AF:

0.00526

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00186

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00162

Gnomad OTH exome

AF:

0.0130

GnomAD4 exome

AF:

0.00778

AC:

11377

AN:

1461894

Hom.:

1019

Cov.:

AF XY:

0.00699

AC XY:

5083

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.237

Gnomad4 AMR exome

AF:

0.0148

Gnomad4 ASJ exome

AF:

0.00455

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.00208

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00104

Gnomad4 OTH exome

AF:

0.0188

GnomAD4 genome

AF:

0.0659

AC:

10030

AN:

152124

Hom.:

1047

Cov.:

AF XY:

0.0643

AC XY:

4780

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.224

Gnomad4 AMR

AF:

0.0304

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.000774

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00150

Gnomad4 OTH

AF:

0.0551

Alfa

AF:

0.0302

Hom.:

343

Bravo

AF:

0.0767

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.226

AC:

997

ESP6500EA

AF:

0.00209

AC:

ExAC

AF:

0.0221

AC:

2688

Asia WGS

AF:

0.0400

AC:

141

AN:

3478

EpiCase

AF:

0.00180

EpiControl

AF:

0.00190

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2021

This variant is associated with the following publications: (PMID: 24555826) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.6

DANN

Benign

0.67

DEOGEN2

Benign

0.039

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.29

MetaRNN

Benign

0.015

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.69

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

0.12

REVEL

Benign

0.024

Sift

Benign

0.62

Sift4G

Benign

0.43

Polyphen

0.0

Vest4

0.0090

MPC

0.40

ClinPred

0.00084

GERP RS

-1.8

Varity_R

0.039

gMVP

0.16

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over