19-42401840-A-C

Position:

chr19-42401840-A-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_005357.4(LIPE):c.3203T>G(p.Val1068Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,453,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

LIPE
NM_005357.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.338

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055652052).

BP6

Variant 19-42401840-A-C is Benign according to our data. Variant chr19-42401840-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3119054.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LIPE	NM_005357.4 linkuse as main transcript	c.3203T>G	p.Val1068Gly	missense_variant	10/10	ENST00000244289.9
LIPE-AS1	NR_073180.1 linkuse as main transcript	n.77+4616A>C		intron_variant, non_coding_transcript_variant
LOC101930071	NR_126041.1 linkuse as main transcript	n.97+4616A>C		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.3203T>G	p.Val1068Gly	missense_variant	10/10	1	NM_005357.4	P1	Q05469-1
LIPE-AS1	ENST00000594624.7 linkuse as main transcript	n.66+4616A>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0000139

AC:

AN:

144086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000521

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000114

AC:

AN:

87748

Hom.:

AF XY:

0.0000202

AC XY:

AN XY:

49448

show subpopulations

Gnomad AFR exome

AF:

0.000325

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000122

AC:

AN:

1309730

Hom.:

Cov.:

AF XY:

0.0000109

AC XY:

AN XY:

643628

show subpopulations

Gnomad4 AFR exome

AF:

0.000185

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000965

Gnomad4 OTH exome

AF:

0.0000185

GnomAD4 genome

AF:

0.0000139

AC:

AN:

144086

Hom.:

Cov.:

AF XY:

0.0000143

AC XY:

AN XY:

69938

show subpopulations

Gnomad4 AFR

AF:

0.0000521

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

9.5

DANN

Benign

0.75

DEOGEN2

Benign

0.059

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0051

LIST_S2

Benign

0.15

M_CAP

Benign

0.0019

MetaRNN

Benign

0.056

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.46

REVEL

Benign

0.058

Sift

Uncertain

0.0040

Sift4G

Pathogenic

0.0

Polyphen

0.0

Vest4

0.079

MutPred

0.24

Loss of stability (P = 0.014);

MVP

0.28

MPC

0.40

ClinPred

0.13

GERP RS

1.9

Varity_R

0.060

gMVP

0.28

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