3-185512408-C-G

Position:

• chr3-185512408-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139248.3(LIPH):​c.1095-711G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,290 control chromosomes in the GnomAD database, including 13,365 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.42 (13365 hom., cov: 29)
• Consequence: LIPH NM_139248.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPH	NM_139248.3	c.1095-711G>C		intron_variant		ENST00000296252.9	NP_640341.1
LIPH	XM_006713529.5	c.1005-711G>C		intron_variant			XP_006713592.1
LIPH	XM_017005852.3	c.993-711G>C		intron_variant			XP_016861341.1
LIPH	XM_011512530.4	c.966-711G>C		intron_variant			XP_011510832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPH	ENST00000296252.9	c.1095-711G>C		intron_variant		1	NM_139248.3	ENSP00000296252.4
LIPH	ENST00000424591.6	c.993-711G>C		intron_variant		1		ENSP00000396384.2
LIPH	ENST00000435679.1	c.126-812G>C		intron_variant		5		ENSP00000390228.1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63208 AN: 151200 Hom.: 13353 Cov.: 29

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.428

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.418 AC: 63244 AN: 151290 Hom.: 13365 Cov.: 29 AF XY: 0.414 AC XY: 30567 AN XY: 73780

Gnomad4 AFR AF: 0.405

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.453

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.430

Alfa AF: 0.416 Hom.: 1715

Bravo AF: 0.420

Asia WGS AF: 0.314 AC: 1092 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.25
DANN	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs12233623; hg19: chr3-185230196;