chr19-42402119-G-C

Variant names:

• chr19-42402119-G-C
• rs35595562
• NM_005357.4:c.2968-44C>G

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.2968-44C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0979 in 1,423,346 control chromosomes in the GnomAD database, including 7,663 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.082 (648 hom., cov: 31)
  • Exomes 𝑓: 0.10 (7015 hom.)
• Consequence: LIPE NM_005357.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0890
• Publications: 3 publications found

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=-0.83).
• BP6: Variant 19-42402119-G-C is Benign according to our data. Variant chr19-42402119-G-C is described in ClinVar as Benign. ClinVar VariationId is 1224184.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005357.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPE	NM_005357.4	MANE Select	c.2968-44C>G		intron	N/A	NP_005348.2
	LIPE	NM_001416100.1		c.2218-44C>G		intron	N/A	NP_001403029.1
	LIPE	NM_001416101.1		c.2203-44C>G		intron	N/A	NP_001403030.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPE	ENST00000244289.9	TSL:1 MANE Select	c.2968-44C>G		intron	N/A	ENSP00000244289.3	Q05469-1
	LIPE-AS1	ENST00000594624.8	TSL:1	n.105+4895G>C		intron	N/A
	LIPE	ENST00000599918.2	TSL:5	c.2992-44C>G		intron	N/A	ENSP00000472218.2	M0R201

Frequencies

GnomAD3 genomes AF: 0.0825 AC: 12544 AN: 152130 Hom.: 652 Cov.: 31

Gnomad AFR AF: 0.0318

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: 0.0739

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.0986

Gnomad OTH AF: 0.0929

GnomAD2 exomes AF: 0.120 AC: 5293 AN: 43960 AF XY: 0.123

Gnomad AFR exome AF: 0.0333

Gnomad AMR exome AF: 0.155

Gnomad ASJ exome AF: 0.111

Gnomad EAS exome AF: 0.0463

Gnomad FIN exome AF: 0.0750

Gnomad NFE exome AF: 0.127

Gnomad OTH exome AF: 0.113

GnomAD4 exome AF: 0.0998 AC: 126798 AN: 1271098 Hom.: 7015 Cov.: 34 AF XY: 0.102 AC XY: 62843 AN XY: 615496

African (AFR) AF: 0.0301 AC: 759 AN: 25230

American (AMR) AF: 0.143 AC: 2739 AN: 19164

Ashkenazi Jewish (ASJ) AF: 0.0897 AC: 1645 AN: 18330

East Asian (EAS) AF: 0.0308 AC: 922 AN: 29952

South Asian (SAS) AF: 0.186 AC: 11394 AN: 61162

European-Finnish (FIN) AF: 0.0703 AC: 3018 AN: 42922

Middle Eastern (MID) AF: 0.190 AC: 743 AN: 3916

European-Non Finnish (NFE) AF: 0.0985 AC: 100267 AN: 1017858

Other (OTH) AF: 0.101 AC: 5311 AN: 52564

GnomAD4 genome AF: 0.0823 AC: 12530 AN: 152248 Hom.: 648 Cov.: 31 AF XY: 0.0841 AC XY: 6261 AN XY: 74444

African (AFR) AF: 0.0318 AC: 1321 AN: 41560

American (AMR) AF: 0.125 AC: 1906 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0914 AC: 317 AN: 3470

East Asian (EAS) AF: 0.0406 AC: 210 AN: 5170

South Asian (SAS) AF: 0.195 AC: 941 AN: 4830

European-Finnish (FIN) AF: 0.0739 AC: 784 AN: 10612

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.0985 AC: 6700 AN: 67992

Other (OTH) AF: 0.0915 AC: 193 AN: 2110

Alfa AF: 0.0909 Hom.: 82

Bravo AF: 0.0835

Asia WGS AF: 0.115 AC: 402 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.9
DANN	Benign	0.38
PhyloP100		0.089
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

Other links and lift over

dbSNP: rs35595562; hg19: chr19-42906271;