Variant 3-185511657-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS1

The NM_139248.3(LIPH):c.1135C>T(p.Leu379Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000249 in 1,613,448 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00026 ( 8 hom. )

Consequence

LIPH
NM_139248.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.70

Variant links:

Genes affected

LIPH (HGNC:18483): (lipase H) This gene encodes a membrane-bound member of the mammalian triglyceride lipase family. It catalyzes the production of 2-acyl lysophosphatidic acid (LPA), which is a lipid mediator with diverse biological properties that include platelet aggregation, smooth muscle contraction, and stimulation of cell proliferation and motility. [provided by RefSeq, Jul 2008]

LIPH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP6

Variant 3-185511657-G-A is Benign according to our data. Variant chr3-185511657-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 288240.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000259 (378/1461246) while in subpopulation SAS AF= 0.00412 (355/86248). AF 95% confidence interval is 0.00376. There are 8 homozygotes in gnomad4_exome. There are 274 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LIPH	NM_139248.3 linkuse as main transcript	c.1135C>T	p.Leu379Phe	missense_variant	9/10	ENST00000296252.9
LIPH	XM_006713529.5 linkuse as main transcript	c.1045C>T	p.Leu349Phe	missense_variant	8/9
LIPH	XM_017005852.3 linkuse as main transcript	c.1033C>T	p.Leu345Phe	missense_variant	8/9
LIPH	XM_011512530.4 linkuse as main transcript	c.1006C>T	p.Leu336Phe	missense_variant	10/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
LIPH	ENST00000296252.9 linkuse as main transcript	c.1135C>T	p.Leu379Phe	missense_variant	9/10	1	NM_139248.3	P1
LIPH	ENST00000424591.6 linkuse as main transcript	c.1033C>T	p.Leu345Phe	missense_variant	8/9	1
LIPH	ENST00000435679.1 linkuse as main transcript	c.128-61C>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00477

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000573

AC:

144

AN:

251462

Hom.:

AF XY:

0.000743

AC XY:

101

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00451

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000259

AC:

378

AN:

1461246

Hom.:

Cov.:

AF XY:

0.000377

AC XY:

274

AN XY:

727000

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00412

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.000151

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00477

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000492

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.000725

AC:

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

May 17, 2016

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Apr 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

0.0

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.50

T;T

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.061

MetaRNN

Benign

0.016

T;T

MetaSVM

Uncertain

0.64

MutationAssessor

Pathogenic

3.0

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.2

D;D

REVEL

Uncertain

0.63

Sift

Benign

0.038

D;D

Sift4G

Benign

0.068

T;T

Polyphen

0.99

D;D

Vest4

0.62

MutPred

0.53

Gain of sheet (P = 0.039);.;

MVP

0.98

MPC

0.29

ClinPred

0.13

GERP RS

5.1

Varity_R

0.43

gMVP

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.22

Position offset: 40

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over