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GeneBe

3-185511676-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_139248.3(LIPH):c.1116A>G(p.Lys372=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 1,609,114 control chromosomes in the GnomAD database, including 145,189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 12707 hom., cov: 31)
Exomes 𝑓: 0.42 ( 132482 hom. )

Consequence

LIPH
NM_139248.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.266
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-185511676-T-C is Benign according to our data. Variant chr3-185511676-T-C is described in ClinVar as [Benign]. Clinvar id is 1228610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-185511676-T-C is described in Lovd as [Benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.266 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LIPHNM_139248.3 linkuse as main transcriptc.1116A>G p.Lys372= synonymous_variant 9/10 ENST00000296252.9
LIPHXM_006713529.5 linkuse as main transcriptc.1026A>G p.Lys342= synonymous_variant 8/9
LIPHXM_017005852.3 linkuse as main transcriptc.1014A>G p.Lys338= synonymous_variant 8/9
LIPHXM_011512530.4 linkuse as main transcriptc.987A>G p.Lys329= synonymous_variant 10/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LIPHENST00000296252.9 linkuse as main transcriptc.1116A>G p.Lys372= synonymous_variant 9/101 NM_139248.3 P1
LIPHENST00000424591.6 linkuse as main transcriptc.1014A>G p.Lys338= synonymous_variant 8/91
LIPHENST00000435679.1 linkuse as main transcriptc.128-80A>G intron_variant 5

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.405
AC:
61461
AN:
151768
Hom.:
12697
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.357
Gnomad AMI
AF:
0.564
Gnomad AMR
AF:
0.408
Gnomad ASJ
AF:
0.452
Gnomad EAS
AF:
0.298
Gnomad SAS
AF:
0.262
Gnomad FIN
AF:
0.415
Gnomad MID
AF:
0.475
Gnomad NFE
AF:
0.445
Gnomad OTH
AF:
0.424
GnomAD3 exomes
AF:
0.397
AC:
99697
AN:
251386
Hom.:
20212
AF XY:
0.395
AC XY:
53739
AN XY:
135878
show subpopulations
Gnomad AFR exome
AF:
0.355
Gnomad AMR exome
AF:
0.364
Gnomad ASJ exome
AF:
0.439
Gnomad EAS exome
AF:
0.296
Gnomad SAS exome
AF:
0.288
Gnomad FIN exome
AF:
0.403
Gnomad NFE exome
AF:
0.452
Gnomad OTH exome
AF:
0.422
GnomAD4 exome
AF:
0.422
AC:
615654
AN:
1457228
Hom.:
132482
Cov.:
34
AF XY:
0.419
AC XY:
304183
AN XY:
725244
show subpopulations
Gnomad4 AFR exome
AF:
0.357
Gnomad4 AMR exome
AF:
0.371
Gnomad4 ASJ exome
AF:
0.432
Gnomad4 EAS exome
AF:
0.306
Gnomad4 SAS exome
AF:
0.287
Gnomad4 FIN exome
AF:
0.408
Gnomad4 NFE exome
AF:
0.442
Gnomad4 OTH exome
AF:
0.410
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.405
AC:
61490
AN:
151886
Hom.:
12707
Cov.:
31
AF XY:
0.402
AC XY:
29860
AN XY:
74226
show subpopulations
Gnomad4 AFR
AF:
0.357
Gnomad4 AMR
AF:
0.407
Gnomad4 ASJ
AF:
0.452
Gnomad4 EAS
AF:
0.298
Gnomad4 SAS
AF:
0.262
Gnomad4 FIN
AF:
0.415
Gnomad4 NFE
AF:
0.445
Gnomad4 OTH
AF:
0.426
Alfa
AF:
0.434
Hom.:
20525
Bravo
AF:
0.405
Asia WGS
AF:
0.311
AC:
1082
AN:
3478
EpiCase
AF:
0.447
EpiControl
AF:
0.459

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -
Benign, criteria provided, single submitterclinical testingGeneDxNov 12, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.53
Cadd
Benign
6.5
Dann
Benign
0.72

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

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.

Other links and lift over

dbSNP: rs61730237; hg19: chr3-185229464; COSMIC: COSV56183240; API