Genetic Variant NM_139248.3:c.1095-272G>A (chr3-185511969-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.97

Publications

6 publications found

Variant links:

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

LIPH links:

TMEM41A-DT (HGNC:58335):

TMEM41A-DT links:

ENSG00000309120 (HGNC:):

ENSG00000309120 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	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

Gene	Transcript	Tags	HGVSc	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.:

show subpopulations

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.:

AF XY:

0.432

AC XY:

32037

AN XY:

74126

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1849

3698

5548

7397

9246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

602

1204

1806

2408

3010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.023

(source)

DANN

Benign

0.56

PhyloP100

-3.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over