rs34623222

chr19-42410613-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2 BP4_Strong BP6_Very_Strong BP7

The NM_005357.4(LIPE):c.1113C>T(p.Asn371=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,613,340 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 0.00081 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (1 hom.)
• Consequence: LIPE NM_005357.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.971

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)

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 19-42410613-G-A is Benign according to our data. Variant chr19-42410613-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 435765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.971 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPE	NM_005357.4	c.1113C>T	p.Asn371=	synonymous_variant	2/10	ENST00000244289.9
LIPE-AS1	NR_073180.1	n.77+13389G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPE	ENST00000244289.9	c.1113C>T	p.Asn371=	synonymous_variant	2/10	1	NM_005357.4	P1
LIPE-AS1	ENST00000594624.7	n.66+13389G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.000808 AC: 123 AN: 152162 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00100

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000752 AC: 187 AN: 248696 Hom.: 1 AF XY: 0.000743 AC XY: 100 AN XY: 134678

Gnomad AFR exome AF: 0.000374

Gnomad AMR exome AF: 0.000406

Gnomad ASJ exome AF: 0.000399

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00108

Gnomad FIN exome AF: 0.0000953

Gnomad NFE exome AF: 0.00102

Gnomad OTH exome AF: 0.00230

GnomAD4 exome AF: 0.00116 AC: 1698 AN: 1461060 Hom.: 1 Cov.: 32 AF XY: 0.00120 AC XY: 869 AN XY: 726900

Gnomad4 AFR exome AF: 0.000269

Gnomad4 AMR exome AF: 0.000447

Gnomad4 ASJ exome AF: 0.000191

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00109

Gnomad4 FIN exome AF: 0.000246

Gnomad4 NFE exome AF: 0.00131

Gnomad4 OTH exome AF: 0.00109

GnomAD4 genome AF: 0.000808 AC: 123 AN: 152280 Hom.: 0 Cov.: 33 AF XY: 0.000913 AC XY: 68 AN XY: 74460

Gnomad4 AFR AF: 0.000361

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00100

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00121 Hom.: 1

Bravo AF: 0.000744

EpiCase AF: 0.00120

EpiControl AF: 0.000771

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Oct 03, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

LIPE: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	0.31
Dann	Benign	0.65

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: rs34623222; hg19: chr19-42914765; COSMIC: COSV99733696; COSMIC: COSV99733696;