19-42402121-C-G

Variant names:

• chr19-42402121-C-G
• rs35639038
• NM_005357.4:c.2968-46G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005357.4(LIPE):​c.2968-46G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.098 in 1,420,750 control chromosomes in the GnomAD database, including 7,656 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.082 (649 hom., cov: 31)
  • Exomes 𝑓: 0.10 (7007 hom.)
• Consequence: LIPE NM_005357.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0160

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 19-42402121-C-G is Benign according to our data. Variant chr19-42402121-C-G is described in ClinVar as [Benign]. Clinvar id is 1234041.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPE	NM_005357.4	c.2968-46G>C		intron_variant	Intron 9 of 9	ENST00000244289.9	NP_005348.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPE	ENST00000244289.9	c.2968-46G>C		intron_variant	Intron 9 of 9	1	NM_005357.4	ENSP00000244289.3

Frequencies

GnomAD3 genomes AF: 0.0825 AC: 12546 AN: 152074 Hom.: 653 Cov.: 31

Gnomad AFR AF: 0.0319

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.0914

Gnomad EAS AF: 0.0407

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.0740

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.0986

Gnomad OTH AF: 0.0934

GnomAD2 exomes AF: 0.121 AC: 5185 AN: 42746 AF XY: 0.123

Gnomad AFR exome AF: 0.0346

Gnomad AMR exome AF: 0.158

Gnomad ASJ exome AF: 0.110

Gnomad EAS exome AF: 0.0468

Gnomad FIN exome AF: 0.0741

Gnomad NFE exome AF: 0.128

Gnomad OTH exome AF: 0.114

GnomAD4 exome AF: 0.0998 AC: 126655 AN: 1268558 Hom.: 7007 Cov.: 34 AF XY: 0.102 AC XY: 62769 AN XY: 614198

Gnomad4 AFR exome AF: 0.0301 AC: 758 AN: 25152

Gnomad4 AMR exome AF: 0.144 AC: 2730 AN: 18908

Gnomad4 ASJ exome AF: 0.0899 AC: 1642 AN: 18256

Gnomad4 EAS exome AF: 0.0309 AC: 920 AN: 29772

Gnomad4 SAS exome AF: 0.187 AC: 11379 AN: 60978

Gnomad4 FIN exome AF: 0.0702 AC: 3004 AN: 42778

Gnomad4 NFE exome AF: 0.0986 AC: 100181 AN: 1016384

Gnomad4 Remaining exome AF: 0.101 AC: 5303 AN: 52434

GnomAD4 genome AF: 0.0823 AC: 12532 AN: 152192 Hom.: 649 Cov.: 31 AF XY: 0.0842 AC XY: 6263 AN XY: 74410

Gnomad4 AFR AF: 0.0318 AC: 0.0318232 AN: 0.0318232

Gnomad4 AMR AF: 0.125 AC: 0.124641 AN: 0.124641

Gnomad4 ASJ AF: 0.0914 AC: 0.0913545 AN: 0.0913545

Gnomad4 EAS AF: 0.0406 AC: 0.0406347 AN: 0.0406347

Gnomad4 SAS AF: 0.195 AC: 0.194905 AN: 0.194905

Gnomad4 FIN AF: 0.0740 AC: 0.0739623 AN: 0.0739623

Gnomad4 NFE AF: 0.0986 AC: 0.0985582 AN: 0.0985582

Gnomad4 OTH AF: 0.0919 AC: 0.0919431 AN: 0.0919431

Alfa AF: 0.0907 Hom.: 89

Bravo AF: 0.0835

Asia WGS AF: 0.115 AC: 402 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 20, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.9
DANN	Benign	0.55
Mutation Taster		=100/0	polymorphism (auto)

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: rs35639038; hg19: chr19-42906273;