NM_005357.4:c.3090G>C

Variant names:

• chr19-42401953-C-G
• rs1800537
• NM_005357.4:c.3090G>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_005357.4(LIPE):​c.3090G>C​(p.Ala1030Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,557,758 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00055 (1 hom., cov: 31)
  • Exomes 𝑓: 0.000057 (0 hom.)
• Consequence: LIPE NM_005357.4 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.13
• Publications: 1 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 19-42401953-C-G is Benign according to our data. Variant chr19-42401953-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3036490.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.13 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.3090G>C	p.Ala1030Ala	synonymous	Exon 10 of 10	NP_005348.2
	LIPE	NM_001416100.1		c.2340G>C	p.Ala780Ala	synonymous	Exon 10 of 10	NP_001403029.1
	LIPE	NM_001416101.1		c.2325G>C	p.Ala775Ala	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.3090G>C	p.Ala1030Ala	synonymous	Exon 10 of 10	ENSP00000244289.3	Q05469-1
	LIPE-AS1	ENST00000594624.8	TSL:1	n.105+4729C>G		intron	N/A
	LIPE	ENST00000599918.2	TSL:5	c.3114G>C	p.Ala1038Ala	synonymous	Exon 10 of 10	ENSP00000472218.2	M0R201

Frequencies

GnomAD3 genomes AF: 0.000545 AC: 83 AN: 152180 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00195

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000163 AC: 25 AN: 153738 AF XY: 0.000142

Gnomad AFR exome AF: 0.00300

Gnomad AMR exome AF: 0.000117

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000569 AC: 80 AN: 1405462 Hom.: 0 Cov.: 36 AF XY: 0.0000547 AC XY: 38 AN XY: 694936

African (AFR) AF: 0.00213 AC: 68 AN: 31866

American (AMR) AF: 0.0000811 AC: 3 AN: 36984

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25036

East Asian (EAS) AF: 0.00 AC: 0 AN: 36842

South Asian (SAS) AF: 0.00 AC: 0 AN: 79868

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4820

European-Non Finnish (NFE) AF: 0.00000184 AC: 2 AN: 1087486

Other (OTH) AF: 0.000120 AC: 7 AN: 58296

GnomAD4 genome AF: 0.000552 AC: 84 AN: 152296 Hom.: 1 Cov.: 31 AF XY: 0.000537 AC XY: 40 AN XY: 74476

African (AFR) AF: 0.00197 AC: 82 AN: 41570

American (AMR) AF: 0.0000653 AC: 1 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68014

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.0000870 Hom.: 0

Bravo AF: 0.000699

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	LIPE-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.9
DANN	Benign	0.63
PhyloP100		-1.1

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: rs1800537; hg19: chr19-42906105;