rs16975750

Positions:

• chr19-42426852-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005357.4(LIPE):​c.298T>C​(p.Tyr100His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 1,614,018 control chromosomes in the GnomAD database, including 2,066 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.066 (1047 hom., cov: 31)
  • Exomes 𝑓: 0.0078 (1019 hom.)
• Consequence: LIPE NM_005357.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.208

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014833629).
• BP6: Variant 19-42426852-A-G is Benign according to our data. Variant chr19-42426852-A-G is described in ClinVar as [Benign]. Clinvar id is 1243216.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPE	NM_005357.4	c.298T>C	p.Tyr100His	missense_variant	1/10	ENST00000244289.9	NP_005348.2
LIPE-AS1	NR_073180.1	n.77+29628A>G		intron_variant, non_coding_transcript_variant
LIPE	XM_005258937.4	c.298T>C	p.Tyr100His	missense_variant	1/9		XP_005258994.1
LIPE-AS1	NR_073179.1	n.1450+1648A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPE	ENST00000244289.9	c.298T>C	p.Tyr100His	missense_variant	1/10	1	NM_005357.4	ENSP00000244289	P1
LIPE-AS1	ENST00000594624.7	n.66+29628A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0656 AC: 9977 AN: 152006 Hom.: 1037 Cov.: 31

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0305

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00150

Gnomad OTH AF: 0.0533

GnomAD3 exomes AF: 0.0185 AC: 4643 AN: 251452 Hom.: 477 AF XY: 0.0135 AC XY: 1828 AN XY: 135902

Gnomad AFR exome AF: 0.234

Gnomad AMR exome AF: 0.0134

Gnomad ASJ exome AF: 0.00526

Gnomad EAS exome AF: 0.000272

Gnomad SAS exome AF: 0.00186

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00162

Gnomad OTH exome AF: 0.0130

GnomAD4 exome AF: 0.00778 AC: 11377 AN: 1461894 Hom.: 1019 Cov.: 32 AF XY: 0.00699 AC XY: 5083 AN XY: 727248

Gnomad4 AFR exome AF: 0.237

Gnomad4 AMR exome AF: 0.0148

Gnomad4 ASJ exome AF: 0.00455

Gnomad4 EAS exome AF: 0.000277

Gnomad4 SAS exome AF: 0.00208

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00104

Gnomad4 OTH exome AF: 0.0188

GnomAD4 genome AF: 0.0659 AC: 10030 AN: 152124 Hom.: 1047 Cov.: 31 AF XY: 0.0643 AC XY: 4780 AN XY: 74396

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.0304

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.000774

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00150

Gnomad4 OTH AF: 0.0551

Alfa AF: 0.0302 Hom.: 343

Bravo AF: 0.0767

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00259 AC: 10

ESP6500AA AF: 0.226 AC: 997

ESP6500EA AF: 0.00209 AC: 18

ExAC AF: 0.0221 AC: 2688

Asia WGS AF: 0.0400 AC: 141 AN: 3478

EpiCase AF: 0.00180

EpiControl AF: 0.00190

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	This variant is associated with the following publications: (PMID: 24555826) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.6
DANN	Benign	0.67
DEOGEN2	Benign	0.039	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.29	T
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.69	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.12	N
REVEL	Benign	0.024
Sift	Benign	0.62	T
Sift4G	Benign	0.43	T
Polyphen		0.0	B
Vest4		0.0090
MPC		0.40
ClinPred		0.00084	T
GERP RS		-1.8
Varity_R		0.039
gMVP		0.16

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: rs16975750; hg19: chr19-42931004; COSMIC: COSV54922628; COSMIC: COSV54922628;