3-185511969-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_139248.3(LIPH):c.1095-272G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 151,780 control chromosomes in the GnomAD database, including 14,635 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.44 (14635 hom., cov: 30)
• Consequence: LIPH NM_139248.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.97

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 3-185511969-C-T is Benign according to our data. Variant chr3-185511969-C-T is described in ClinVar as [Benign]. Clinvar id is 1240580.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPH	NM_139248.3	c.1095-272G>A		intron_variant		ENST00000296252.9
LIPH	XM_006713529.5	c.1005-272G>A		intron_variant
LIPH	XM_011512530.4	c.966-272G>A		intron_variant
LIPH	XM_017005852.3	c.993-272G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPH	ENST00000296252.9	c.1095-272G>A		intron_variant		1	NM_139248.3	P1
LIPH	ENST00000424591.6	c.993-272G>A		intron_variant		1
LIPH	ENST00000435679.1	c.128-373G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66104 AN: 151662 Hom.: 14614 Cov.: 30

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.474

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.436 AC: 66164 AN: 151780 Hom.: 14635 Cov.: 30 AF XY: 0.432 AC XY: 32037 AN XY: 74126

Gnomad4 AFR AF: 0.464

Gnomad4 AMR AF: 0.419

Gnomad4 ASJ AF: 0.453

Gnomad4 EAS AF: 0.299

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.444

Alfa AF: 0.447 Hom.: 14965

Bravo AF: 0.441

Asia WGS AF: 0.324 AC: 1126 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.023
Dann	Benign	0.56

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: rs12233604; hg19: chr3-185229757; COSMIC: COSV56185840;