19-42423369-T-C

Position:

• chr19-42423369-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005357.4(LIPE):​c.883+2898A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0764 in 1,259,560 control chromosomes in the GnomAD database, including 5,520 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1611 hom., cov: 32)
  • Exomes 𝑓: 0.070 (3909 hom.)
• Consequence: LIPE NM_005357.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.719

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPE	NM_005357.4	c.883+2898A>G		intron_variant		ENST00000244289.9	NP_005348.2
LIPE-AS1	NR_073180.1	n.77+26145T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPE	ENST00000244289.9	c.883+2898A>G		intron_variant		1	NM_005357.4	ENSP00000244289	P1
LIPE-AS1	ENST00000594624.7	n.66+26145T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18364 AN: 152076 Hom.: 1595 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0838

Gnomad EAS AF: 0.0825

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.0461

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.0583

Gnomad OTH AF: 0.115

GnomAD3 exomes AF: 0.106 AC: 14135 AN: 133740 Hom.: 954 AF XY: 0.104 AC XY: 7593 AN XY: 72868

Gnomad AFR exome AF: 0.257

Gnomad AMR exome AF: 0.152

Gnomad ASJ exome AF: 0.0809

Gnomad EAS exome AF: 0.100

Gnomad SAS exome AF: 0.149

Gnomad FIN exome AF: 0.0405

Gnomad NFE exome AF: 0.0591

Gnomad OTH exome AF: 0.0984

GnomAD4 exome AF: 0.0703 AC: 77821 AN: 1107366 Hom.: 3909 Cov.: 19 AF XY: 0.0726 AC XY: 39537 AN XY: 544832

Gnomad4 AFR exome AF: 0.267

Gnomad4 AMR exome AF: 0.152

Gnomad4 ASJ exome AF: 0.0803

Gnomad4 EAS exome AF: 0.0959

Gnomad4 SAS exome AF: 0.144

Gnomad4 FIN exome AF: 0.0419

Gnomad4 NFE exome AF: 0.0544

Gnomad4 OTH exome AF: 0.0893

GnomAD4 genome AF: 0.121 AC: 18423 AN: 152194 Hom.: 1611 Cov.: 32 AF XY: 0.122 AC XY: 9043 AN XY: 74404

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.0838

Gnomad4 EAS AF: 0.0823

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.0461

Gnomad4 NFE AF: 0.0583

Gnomad4 OTH AF: 0.117

Alfa AF: 0.0611 Hom.: 99

Bravo AF: 0.134

Asia WGS AF: 0.144 AC: 501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	9.3
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10422283; hg19: chr19-42927521; COSMIC: COSV54923044; COSMIC: COSV54923044;