3-185508608-A-G

Variant names:

• chr3-185508608-A-G
• rs6788865
• NM_139248.3:c.*182T>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_139248.3(LIPH):​c.*182T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 613,392 control chromosomes in the GnomAD database, including 53,832 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (13639 hom., cov: 34)
  • Exomes 𝑓: 0.41 (40193 hom.)
• Consequence: LIPH NM_139248.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.208

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-185508608-A-G is Benign according to our data. Variant chr3-185508608-A-G is described in ClinVar as [Benign]. Clinvar id is 1179532.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: 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 rank	MANE	Protein	UniProt
LIPH	NM_139248.3	c.*182T>C		3_prime_UTR_variant	Exon 10 of 10	ENST00000296252.9	NP_640341.1
LIPH	XM_006713529.5	c.*182T>C		3_prime_UTR_variant	Exon 9 of 9		XP_006713592.1
LIPH	XM_017005852.3	c.*182T>C		3_prime_UTR_variant	Exon 9 of 9		XP_016861341.1
LIPH	XM_011512530.4	c.*182T>C		3_prime_UTR_variant	Exon 11 of 11		XP_011510832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPH	ENST00000296252	c.*182T>C		3_prime_UTR_variant	Exon 10 of 10	1	NM_139248.3	ENSP00000296252.4
LIPH	ENST00000424591	c.*182T>C		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000396384.2
LIPH	ENST00000435679.1	c.*249T>C		3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000390228.1

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63960 AN: 152036 Hom.: 13627 Cov.: 34

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.430

GnomAD4 exome AF: 0.411 AC: 189381 AN: 461238 Hom.: 40193 Cov.: 4 AF XY: 0.403 AC XY: 99605 AN XY: 247018

Gnomad4 AFR exome AF: 0.409

Gnomad4 AMR exome AF: 0.384

Gnomad4 ASJ exome AF: 0.430

Gnomad4 EAS exome AF: 0.307

Gnomad4 SAS exome AF: 0.288

Gnomad4 FIN exome AF: 0.408

Gnomad4 NFE exome AF: 0.444

Gnomad4 OTH exome AF: 0.420

GnomAD4 genome AF: 0.421 AC: 63997 AN: 152154 Hom.: 13639 Cov.: 34 AF XY: 0.417 AC XY: 30997 AN XY: 74390

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.453

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.432

Alfa AF: 0.435 Hom.: 14106

Bravo AF: 0.423

Asia WGS AF: 0.314 AC: 1092 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.3
DANN	Benign	0.59

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: rs6788865; hg19: chr3-185226396;