Variant 19-42401871-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005357.4(LIPE):c.3172G>C(p.Gly1058Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000654 in 1,532,144 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00069 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00065 ( 2 hom. )

Consequence

LIPE
NM_005357.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.75

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 made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00461185).

BP6

Variant 19-42401871-C-G is Benign according to our data. Variant chr19-42401871-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 708992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LIPE	NM_005357.4 linkuse as main transcript	c.3172G>C	p.Gly1058Arg	missense_variant	10/10	ENST00000244289.9	NP_005348.2
LIPE-AS1	NR_073180.1 linkuse as main transcript	n.77+4647C>G		intron_variant, non_coding_transcript_variant
LOC101930071	NR_126041.1 linkuse as main transcript	n.97+4647C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPE	ENST00000244289.9 linkuse as main transcript	c.3172G>C	p.Gly1058Arg	missense_variant	10/10	1	NM_005357.4	ENSP00000244289	P1	Q05469-1
LIPE-AS1	ENST00000594624.7 linkuse as main transcript	n.66+4647C>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.000683

AC:

104

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000813

AC:

104

AN:

127974

Hom.:

AF XY:

0.000822

AC XY:

AN XY:

70572

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00161

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00114

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000752

Gnomad OTH exome

AF:

0.00213

GnomAD4 exome

AF:

0.000650

AC:

897

AN:

1379858

Hom.:

Cov.:

AF XY:

0.000664

AC XY:

452

AN XY:

681148

show subpopulations

Gnomad4 AFR exome

AF:

0.000300

Gnomad4 AMR exome

AF:

0.00101

Gnomad4 ASJ exome

AF:

0.00188

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000886

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000589

Gnomad4 OTH exome

AF:

0.00132

GnomAD4 genome

AF:

0.000689

AC:

105

AN:

152286

Hom.:

Cov.:

AF XY:

0.000739

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000794

Hom.:

Bravo

AF:

0.000892

ExAC

AF:

0.000623

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.54

DANN

Benign

0.58

DEOGEN2

Benign

0.039

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.39

MetaRNN

Benign

0.0046

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.69

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.60

PROVEAN

Benign

0.35

REVEL

Benign

0.030

Sift

Benign

0.58

Sift4G

Benign

0.26

Polyphen

0.0

Vest4

0.051

MutPred

0.28

Gain of methylation at G1058 (P = 0.0183);

MVP

0.36

MPC

0.37

ClinPred

0.0092

GERP RS

-3.7

Varity_R

0.041

gMVP

0.17

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