3-185512408-C-G

Variant names:

• chr3-185512408-C-G
• rs12233623
• NM_139248.3:c.1095-711G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

LIPH Gene-Disease associations (from GenCC):

• hypotrichosis 7

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• hypotrichosis simplex

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• isolated familial wooly hair disorder

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TMEM41A-DT (HGNC:58335):

ENSG00000309120 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139248.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPH	NM_139248.3	MANE Select	c.1095-711G>C		intron	N/A	NP_640341.1	Q8WWY8
	LIPH	NM_001438651.1		c.1005-711G>C		intron	N/A	NP_001425580.1
	LIPH	NM_001438029.1		c.993-711G>C		intron	N/A	NP_001424958.1	A2IBA6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPH	ENST00000296252.9	TSL:1 MANE Select	c.1095-711G>C		intron	N/A	ENSP00000296252.4	Q8WWY8
	LIPH	ENST00000424591.6	TSL:1	c.993-711G>C		intron	N/A	ENSP00000396384.2	A2IBA6
	LIPH	ENST00000953488.1		c.1116-711G>C		intron	N/A	ENSP00000623547.1

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

African (AFR) AF: 0.405 AC: 16663 AN: 41170

American (AMR) AF: 0.410 AC: 6234 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 1567 AN: 3462

East Asian (EAS) AF: 0.297 AC: 1520 AN: 5126

South Asian (SAS) AF: 0.262 AC: 1255 AN: 4794

European-Finnish (FIN) AF: 0.414 AC: 4300 AN: 10392

Middle Eastern (MID) AF: 0.479 AC: 139 AN: 290

European-Non Finnish (NFE) AF: 0.444 AC: 30156 AN: 67860

Other (OTH) AF: 0.430 AC: 902 AN: 2096

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.25
DANN	Benign	0.42
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12233623; hg19: chr3-185230196;