rs34052647

Positions:

• chr19-42407617-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005357.4(LIPE):​c.1831C>T​(p.Arg611Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00414 in 1,608,150 control chromosomes in the GnomAD database, including 197 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0067 (22 hom., cov: 32)
  • Exomes 𝑓: 0.0039 (175 hom.)
• Consequence: LIPE NM_005357.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 4.93

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006269008).
• BP6: Variant 19-42407617-G-A is Benign according to our data. Variant chr19-42407617-G-A is described in ClinVar as [Benign]. Clinvar id is 2430297.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPE	NM_005357.4	c.1831C>T	p.Arg611Cys	missense_variant	5/10	ENST00000244289.9
LIPE-AS1	NR_073180.1	n.77+10393G>A		intron_variant, non_coding_transcript_variant
LOC101930071	NR_126041.1	n.98-641G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPE	ENST00000244289.9	c.1831C>T	p.Arg611Cys	missense_variant	5/10	1	NM_005357.4	P1
LIPE-AS1	ENST00000594624.7	n.66+10393G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.00672 AC: 1022 AN: 152144 Hom.: 22 Cov.: 32

Gnomad AFR AF: 0.00174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0373

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.0623

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.0131 AC: 3223 AN: 246066 Hom.: 108 AF XY: 0.0108 AC XY: 1438 AN XY: 132940

Gnomad AFR exome AF: 0.00173

Gnomad AMR exome AF: 0.0542

Gnomad ASJ exome AF: 0.00311

Gnomad EAS exome AF: 0.0639

Gnomad SAS exome AF: 0.00170

Gnomad FIN exome AF: 0.0000468

Gnomad NFE exome AF: 0.000389

Gnomad OTH exome AF: 0.00973

GnomAD4 exome AF: 0.00387 AC: 5637 AN: 1455888 Hom.: 175 Cov.: 32 AF XY: 0.00361 AC XY: 2615 AN XY: 723638

Gnomad4 AFR exome AF: 0.000749

Gnomad4 AMR exome AF: 0.0528

Gnomad4 ASJ exome AF: 0.00260

Gnomad4 EAS exome AF: 0.0617

Gnomad4 SAS exome AF: 0.00199

Gnomad4 FIN exome AF: 0.0000564

Gnomad4 NFE exome AF: 0.000263

Gnomad4 OTH exome AF: 0.00508

GnomAD4 genome AF: 0.00674 AC: 1027 AN: 152262 Hom.: 22 Cov.: 32 AF XY: 0.00789 AC XY: 587 AN XY: 74442

Gnomad4 AFR AF: 0.00173

Gnomad4 AMR AF: 0.0375

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.0625

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00382 Hom.: 23

Bravo AF: 0.0103

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.0108 AC: 1315

Asia WGS AF: 0.0210 AC: 72 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

See cases Benign:1

Benign, criteria provided, single submitter

clinical testing

Institute of Human Genetics, University Hospital Muenster

Dec 21, 2022

ACMG categories: BA1 -

LIPE-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 26, 2019

This variant is classified as 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
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.48	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.99	D
MetaRNN	Benign	0.0063	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.7	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Uncertain	0.39
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.32
MPC		1.2
ClinPred		0.048	T
GERP RS		1.9
Varity_R		0.61
gMVP		0.73

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: rs34052647; hg19: chr19-42911769;