dbSNP rs1183308693: LIPE:p.Arg1017Cys (chr19-42401994-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005357.4(LIPE):c.3049C>T(p.Arg1017Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000713 in 1,402,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1017G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

LIPE
NM_005357.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.60

Publications

0 publications found

Variant links:

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 links:

LIPE-AS1 (HGNC:48589): (LIPE antisense RNA 1)

LIPE-AS1 links:

LOC101930071 (HGNC:):

LOC101930071 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15766063).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LIPE	NM_005357.4	MANE Select	c.3049C>T	p.Arg1017Cys	missense	Exon 10 of 10	NP_005348.2
LIPE	NM_001416100.1		c.2299C>T	p.Arg767Cys	missense	Exon 10 of 10	NP_001403029.1
LIPE	NM_001416101.1		c.2284C>T	p.Arg762Cys	missense	Exon 10 of 10	NP_001403030.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LIPE	ENST00000244289.9	TSL:1 MANE Select	c.3049C>T	p.Arg1017Cys	missense	Exon 10 of 10	ENSP00000244289.3	Q05469-1
LIPE-AS1	ENST00000594624.8	TSL:1	n.105+4770G>A		intron	N/A
LIPE	ENST00000599918.2	TSL:5	c.3073C>T	p.Arg1025Cys	missense	Exon 10 of 10	ENSP00000472218.2	M0R201

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.13e-7

AC:

AN:

1402094

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

692512

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31364

American (AMR)

AF:

0.00

AC:

AN:

36458

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24994

East Asian (EAS)

AF:

0.00

AC:

AN:

36248

South Asian (SAS)

AF:

0.00

AC:

AN:

79446

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46850

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4796

European-Non Finnish (NFE)

AF:

9.23e-7

AC:

AN:

1083856

Other (OTH)

AF:

0.00

AC:

AN:

58082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Uncertain

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.099

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.62

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.017

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.98

PhyloP100

1.6

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.9

REVEL

Benign

0.078

Sift

Benign

0.11

Sift4G

Benign

0.12

Polyphen

0.0040

Vest4

0.092

MutPred

0.68

Loss of MoRF binding (P = 0.0404)

MVP

0.49

MPC

0.44

ClinPred

0.10

GERP RS

2.5

Varity_R

0.12

gMVP

0.37

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over