19-42402121-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005357.4(LIPE):​c.2968-46G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000788 in 1,268,830 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: LIPE NM_005357.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

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.2968-46G>T		intron	N/A	NP_005348.2
	LIPE	NM_001416100.1		c.2218-46G>T		intron	N/A	NP_001403029.1
	LIPE	NM_001416101.1		c.2203-46G>T		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.2968-46G>T		intron	N/A	ENSP00000244289.3	Q05469-1
	LIPE-AS1	ENST00000594624.8	TSL:1	n.105+4897C>A		intron	N/A
	LIPE	ENST00000599918.2	TSL:5	c.2992-46G>T		intron	N/A	ENSP00000472218.2	M0R201

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.88e-7 AC: 1 AN: 1268830 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 614328

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25154

American (AMR) AF: 0.00 AC: 0 AN: 18944

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18260

East Asian (EAS) AF: 0.00 AC: 0 AN: 29772

South Asian (SAS) AF: 0.00 AC: 0 AN: 61006

European-Finnish (FIN) AF: 0.0000234 AC: 1 AN: 42796

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3904

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1016538

Other (OTH) AF: 0.00 AC: 0 AN: 52456

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.7
DANN	Benign	0.70
PhyloP100		0.016

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: rs35639038; hg19: chr19-42906273;