19-42401822-C-G

Position:

• chr19-42401822-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_005357.4(LIPE):​c.3221G>C​(p.Gly1074Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00278 in 1,477,752 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0028 (8 hom.)
• Consequence: LIPE NM_005357.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.38

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00436604).
• BP6: Variant 19-42401822-C-G is Benign according to our data. Variant chr19-42401822-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2650042.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPE	NM_005357.4	c.3221G>C	p.Gly1074Ala	missense_variant	10/10	ENST00000244289.9	NP_005348.2
LIPE-AS1	NR_073180.1	n.77+4598C>G		intron_variant, non_coding_transcript_variant
LOC101930071	NR_126041.1	n.97+4598C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPE	ENST00000244289.9	c.3221G>C	p.Gly1074Ala	missense_variant	10/10	1	NM_005357.4	ENSP00000244289	P1
LIPE-AS1	ENST00000594624.7	n.66+4598C>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.00245 AC: 372 AN: 151734 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000847

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000787

Gnomad ASJ AF: 0.00232

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00229

Gnomad FIN AF: 0.00698

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00339

Gnomad OTH AF: 0.000961

GnomAD3 exomes AF: 0.00317 AC: 266 AN: 83822 Hom.: 3 AF XY: 0.00351 AC XY: 161 AN XY: 45806

Gnomad AFR exome AF: 0.000306

Gnomad AMR exome AF: 0.000200

Gnomad ASJ exome AF: 0.00159

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00177

Gnomad FIN exome AF: 0.00902

Gnomad NFE exome AF: 0.00488

Gnomad OTH exome AF: 0.00292

GnomAD4 exome AF: 0.00281 AC: 3731 AN: 1325906 Hom.: 8 Cov.: 30 AF XY: 0.00273 AC XY: 1781 AN XY: 651486

Gnomad4 AFR exome AF: 0.000505

Gnomad4 AMR exome AF: 0.000611

Gnomad4 ASJ exome AF: 0.00233

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00156

Gnomad4 FIN exome AF: 0.00754

Gnomad4 NFE exome AF: 0.00297

Gnomad4 OTH exome AF: 0.00231

GnomAD4 genome AF: 0.00245 AC: 372 AN: 151846 Hom.: 0 Cov.: 30 AF XY: 0.00268 AC XY: 199 AN XY: 74220

Gnomad4 AFR AF: 0.000845

Gnomad4 AMR AF: 0.000786

Gnomad4 ASJ AF: 0.00232

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00229

Gnomad4 FIN AF: 0.00698

Gnomad4 NFE AF: 0.00339

Gnomad4 OTH AF: 0.000951

Alfa AF: 0.00258 Hom.: 1

Bravo AF: 0.00194

ExAC AF: 0.00241 AC: 212

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2023

LIPE: BS2 -

LIPE-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 17, 2024

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	Benign	0.094
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.0044	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	0.26	N
REVEL	Benign	0.057
Sift	Pathogenic	0.0	D
Polyphen		0.97	D
Vest4		0.12
MVP		0.55
MPC		0.33
ClinPred		0.039	T
GERP RS		2.4
Varity_R		0.062
gMVP		0.20

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: rs201301144; hg19: chr19-42905974;