3-185508704-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.*86G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 972,864 control chromosomes in the GnomAD database, including 34,759 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (4057 hom., cov: 33)
  • Exomes 𝑓: 0.26 (30702 hom.)
• Consequence: LIPH NM_139248.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.815

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=-0.51).
• BP6: Variant 3-185508704-C-T is Benign according to our data. Variant chr3-185508704-C-T is described in ClinVar as [Benign]. Clinvar id is 1178899.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPH	NM_139248.3	c.*86G>A		3_prime_UTR_variant	10/10	ENST00000296252.9
LIPH	XM_006713529.5	c.*86G>A		3_prime_UTR_variant	9/9
LIPH	XM_011512530.4	c.*86G>A		3_prime_UTR_variant	11/11
LIPH	XM_017005852.3	c.*86G>A		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPH	ENST00000296252.9	c.*86G>A		3_prime_UTR_variant	10/10	1	NM_139248.3	P1
LIPH	ENST00000424591.6	c.*86G>A		3_prime_UTR_variant	9/9	1
LIPH	ENST00000435679.1	c.*153G>A		3_prime_UTR_variant	4/4	5

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30628 AN: 152056 Hom.: 4058 Cov.: 33

Gnomad AFR AF: 0.0523

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.225

GnomAD4 exome AF: 0.258 AC: 211975 AN: 820690 Hom.: 30702 Cov.: 11 AF XY: 0.257 AC XY: 111371 AN XY: 432516

Gnomad4 AFR exome AF: 0.0457

Gnomad4 AMR exome AF: 0.128

Gnomad4 ASJ exome AF: 0.310

Gnomad4 EAS exome AF: 0.000708

Gnomad4 SAS exome AF: 0.196

Gnomad4 FIN exome AF: 0.277

Gnomad4 NFE exome AF: 0.299

Gnomad4 OTH exome AF: 0.249

GnomAD4 genome AF: 0.201 AC: 30622 AN: 152174 Hom.: 4057 Cov.: 33 AF XY: 0.198 AC XY: 14694 AN XY: 74378

Gnomad4 AFR AF: 0.0521

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.221

Alfa AF: 0.269 Hom.: 1232

Bravo AF: 0.187

Asia WGS AF: 0.0720 AC: 252 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

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	6.8
Dann	Benign	0.61

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: rs55854644; hg19: chr3-185226492; COSMIC: COSV56183594;