chr19-42401848-A-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_005357.4(LIPE):​c.3195T>G​(p.Ala1065Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000072 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LIPE NM_005357.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 19-42401848-A-C is Benign according to our data. Variant chr19-42401848-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3025791.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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>G	p.Ala1065Ala	synonymous	Exon 10 of 10	NP_005348.2
	LIPE	NM_001416100.1		c.2445T>G	p.Ala815Ala	synonymous	Exon 10 of 10	NP_001403029.1
	LIPE	NM_001416101.1		c.2430T>G	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>G	p.Ala1065Ala	synonymous	Exon 10 of 10	ENSP00000244289.3	Q05469-1
	LIPE-AS1	ENST00000594624.8	TSL:1	n.105+4624A>C		intron	N/A
	LIPE	ENST00000599918.2	TSL:5	c.3219T>G	p.Ala1073Ala	synonymous	Exon 10 of 10	ENSP00000472218.2	M0R201

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000716 AC: 4 AN: 558474 Hom.: 0 Cov.: 24 AF XY: 0.00000705 AC XY: 2 AN XY: 283696

⚠️ 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: 11102

American (AMR) AF: 0.0000580 AC: 1 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: 0.0000187 AC: 1 AN: 53568

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18040

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

European-Non Finnish (NFE) AF: 0.00000484 AC: 2 AN: 413624

Other (OTH) AF: 0.00 AC: 0 AN: 22372

⚠️ 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

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.57
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism

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; COSMIC: COSV105037784; COSMIC: COSV105037784;