3-185511969-C-T

Variant names:

• chr3-185511969-C-T
• rs12233604
• NM_139248.3:c.1095-272G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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 -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 VariationId 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.

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.1095-272G>A		intron	N/A	NP_640341.1	Q8WWY8
	LIPH	NM_001438651.1		c.1005-272G>A		intron	N/A	NP_001425580.1
	LIPH	NM_001438029.1		c.993-272G>A		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.1095-272G>A		intron	N/A	ENSP00000296252.4	Q8WWY8
	LIPH	ENST00000424591.6	TSL:1	c.993-272G>A		intron	N/A	ENSP00000396384.2	A2IBA6
	LIPH	ENST00000953488.1		c.1116-272G>A		intron	N/A	ENSP00000623547.1

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

African (AFR) AF: 0.464 AC: 19191 AN: 41374

American (AMR) AF: 0.419 AC: 6379 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 1573 AN: 3470

East Asian (EAS) AF: 0.299 AC: 1538 AN: 5148

South Asian (SAS) AF: 0.264 AC: 1266 AN: 4802

European-Finnish (FIN) AF: 0.415 AC: 4363 AN: 10502

Middle Eastern (MID) AF: 0.472 AC: 137 AN: 290

European-Non Finnish (NFE) AF: 0.445 AC: 30266 AN: 67942

Other (OTH) AF: 0.444 AC: 937 AN: 2108

Alfa AF: 0.446 Hom.: 19485

Bravo AF: 0.441

Asia WGS AF: 0.324 AC: 1126 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.023
DANN	Benign	0.56
PhyloP100		-3.0
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: rs12233604; hg19: chr3-185229757; COSMIC: COSV56185840;