chr19-42401848-A-G

Variant names:

• chr19-42401848-A-G
• rs1365592686
• NM_005357.4:c.3195T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_005357.4(LIPE):​c.3195T>C​(p.Ala1065Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000537 in 558,508 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. Synonymous variant affecting the same amino acid position (i.e. A1065A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000054 (0 hom.)
• Consequence: LIPE NM_005357.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=-0.101 with no splicing effect.

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.3195T>C	p.Ala1065Ala	synonymous	Exon 10 of 10	NP_005348.2
	LIPE	NM_001416100.1		c.2445T>C	p.Ala815Ala	synonymous	Exon 10 of 10	NP_001403029.1
	LIPE	NM_001416101.1		c.2430T>C	p.Ala810Ala	synonymous	Exon 10 of 10	NP_001403030.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPE	ENST00000244289.9	TSL:1 MANE Select	c.3195T>C	p.Ala1065Ala	synonymous	Exon 10 of 10	ENSP00000244289.3	Q05469-1
	LIPE-AS1	ENST00000594624.8	TSL:1	n.105+4624A>G		intron	N/A
	LIPE	ENST00000599918.2	TSL:5	c.3219T>C	p.Ala1073Ala	synonymous	Exon 10 of 10	ENSP00000472218.2	M0R201

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000537 AC: 3 AN: 558508 Hom.: 0 Cov.: 24 AF XY: 0.0000106 AC XY: 3 AN XY: 283710

African (AFR) AF: 0.00 AC: 0 AN: 11102

American (AMR) AF: 0.00 AC: 0 AN: 17234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10936

East Asian (EAS) AF: 0.00 AC: 0 AN: 9924

South Asian (SAS) AF: 0.00 AC: 0 AN: 53568

European-Finnish (FIN) AF: 0.0000554 AC: 1 AN: 18042

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1674

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 413656

Other (OTH) AF: 0.0000894 AC: 2 AN: 22372

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.52
PhyloP100		-0.10

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: rs1365592686; hg19: chr19-42906000;