rs34052647

Variant names:

• chr19-42407617-G-A
• rs34052647
• NM_005357.4:c.1831C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-42407617-G-A
• chr19-42407617-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005357.4(LIPE):​c.1831C>T​(p.Arg611Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00414 in 1,608,150 control chromosomes in the GnomAD database, including 197 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R611H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0067 (22 hom., cov: 32)
  • Exomes 𝑓: 0.0039 (175 hom.)
• Consequence: LIPE NM_005357.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 4.93
• Publications: 10 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006269008).
• BP6: Variant 19-42407617-G-A is Benign according to our data. Variant chr19-42407617-G-A is described in ClinVar as Benign. ClinVar VariationId is 2430297.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0569 is higher than 0.05.

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.1831C>T	p.Arg611Cys	missense	Exon 5 of 10	NP_005348.2
	LIPE	NM_001416100.1		c.1081C>T	p.Arg361Cys	missense	Exon 5 of 10	NP_001403029.1
	LIPE	NM_001416101.1		c.1066C>T	p.Arg356Cys	missense	Exon 5 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.1831C>T	p.Arg611Cys	missense	Exon 5 of 10	ENSP00000244289.3	Q05469-1
	LIPE-AS1	ENST00000594624.8	TSL:1	n.105+10393G>A		intron	N/A
	LIPE	ENST00000599918.2	TSL:5	c.1831C>T	p.Arg611Cys	missense	Exon 5 of 10	ENSP00000472218.2	M0R201

Frequencies

GnomAD3 genomes AF: 0.00672 AC: 1022 AN: 152144 Hom.: 22 Cov.: 32

Gnomad AFR AF: 0.00174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0373

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.0623

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.0131 AC: 3223 AN: 246066 AF XY: 0.0108

Gnomad AFR exome AF: 0.00173

Gnomad AMR exome AF: 0.0542

Gnomad ASJ exome AF: 0.00311

Gnomad EAS exome AF: 0.0639

Gnomad FIN exome AF: 0.0000468

Gnomad NFE exome AF: 0.000389

Gnomad OTH exome AF: 0.00973

GnomAD4 exome AF: 0.00387 AC: 5637 AN: 1455888 Hom.: 175 Cov.: 32 AF XY: 0.00361 AC XY: 2615 AN XY: 723638

African (AFR) AF: 0.000749 AC: 25 AN: 33358

American (AMR) AF: 0.0528 AC: 2326 AN: 44028

Ashkenazi Jewish (ASJ) AF: 0.00260 AC: 67 AN: 25770

East Asian (EAS) AF: 0.0617 AC: 2446 AN: 39614

South Asian (SAS) AF: 0.00199 AC: 170 AN: 85574

European-Finnish (FIN) AF: 0.0000564 AC: 3 AN: 53232

Middle Eastern (MID) AF: 0.000522 AC: 3 AN: 5746

European-Non Finnish (NFE) AF: 0.000263 AC: 292 AN: 1108514

Other (OTH) AF: 0.00508 AC: 305 AN: 60052

GnomAD4 genome AF: 0.00674 AC: 1027 AN: 152262 Hom.: 22 Cov.: 32 AF XY: 0.00789 AC XY: 587 AN XY: 74442

African (AFR) AF: 0.00173 AC: 72 AN: 41554

American (AMR) AF: 0.0375 AC: 574 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3472

East Asian (EAS) AF: 0.0625 AC: 323 AN: 5170

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68010

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.00414 Hom.: 44

Bravo AF: 0.0103

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.0108 AC: 1315

Asia WGS AF: 0.0210 AC: 72 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.48	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.99	D
MetaRNN	Benign	0.0063	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		4.9
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Uncertain	0.39
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.32
MPC		1.2
ClinPred		0.048	T
GERP RS		1.9
PromoterAI		-0.027	Neutral
Varity_R		0.61
gMVP		0.73
Mutation Taster		=89/11	polymorphism (auto)

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: rs34052647; hg19: chr19-42911769;