rs2277892

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_022773.4(LMF1):c.540G>A(p.Thr180Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,611,352 control chromosomes in the GnomAD database, including 18,712 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 4241 hom., cov: 32)

Exomes 𝑓: 0.12 ( 14471 hom. )

Consequence

LMF1
NM_022773.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.63

Publications

24 publications found

Variant links:

Genes affected

LMF1 (HGNC:14154): (lipase maturation factor 1) Involved in triglyceride metabolic process. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum membrane. Implicated in familial lipase maturation factor 1 deficiency. [provided by Alliance of Genome Resources, Apr 2022]

LMF1 Gene-Disease associations (from GenCC):

lipase deficiency, combined
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics

LMF1 links:

LOC124903619 (HGNC:):

LOC124903619 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 16-911054-C-T is Benign according to our data. Variant chr16-911054-C-T is described in ClinVar as Benign. ClinVar VariationId is 1247993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.63 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMF1	NM_022773.4 link	c.540G>A	p.Thr180Thr	synonymous_variant	Exon 4 of 11	ENST00000262301.16	NP_073610.2	Q96S06-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMF1	ENST00000262301.16 link	c.540G>A	p.Thr180Thr	synonymous_variant	Exon 4 of 11	5	NM_022773.4	ENSP00000262301.12		Q96S06-1

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30374

AN:

151912

Hom.:

4221

Cov.:

show subpopulations

Gnomad AFR

AF:

0.377

Gnomad AMI

AF:

0.202

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.242

Gnomad SAS

AF:

0.234

Gnomad FIN

AF:

0.0549

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.177

GnomAD2 exomes

AF:

0.168

AC:

41289

AN:

245772

AF XY:

0.162

show subpopulations

Gnomad AFR exome

AF:

0.380

Gnomad AMR exome

AF:

0.288

Gnomad ASJ exome

AF:

0.102

Gnomad EAS exome

AF:

0.250

Gnomad FIN exome

AF:

0.0567

Gnomad NFE exome

AF:

0.103

Gnomad OTH exome

AF:

0.144

GnomAD4 exome

AF:

0.124

AC:

181604

AN:

1459324

Hom.:

14471

Cov.:

AF XY:

0.126

AC XY:

91474

AN XY:

725868

show subpopulations

African (AFR)

AF:

0.388

AC:

12960

AN:

33424

American (AMR)

AF:

0.283

AC:

12547

AN:

44332

Ashkenazi Jewish (ASJ)

AF:

0.109

AC:

2835

AN:

26128

East Asian (EAS)

AF:

0.224

AC:

8886

AN:

39592

South Asian (SAS)

AF:

0.223

AC:

19152

AN:

86056

European-Finnish (FIN)

AF:

0.0603

AC:

3174

AN:

52638

Middle Eastern (MID)

AF:

0.107

AC:

617

AN:

5768

European-Non Finnish (NFE)

AF:

0.102

AC:

113258

AN:

1111074

Other (OTH)

AF:

0.136

AC:

8175

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

7737

15473

23210

30946

38683

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4442

8884

13326

17768

22210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.200

AC:

30440

AN:

152028

Hom.:

4241

Cov.:

AF XY:

0.199

AC XY:

14815

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.377

AC:

15617

AN:

41402

American (AMR)

AF:

0.240

AC:

3662

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.111

AC:

385

AN:

3468

East Asian (EAS)

AF:

0.242

AC:

1251

AN:

5168

South Asian (SAS)

AF:

0.234

AC:

1128

AN:

4814

European-Finnish (FIN)

AF:

0.0549

AC:

582

AN:

10592

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.106

AC:

7235

AN:

67994

Other (OTH)

AF:

0.176

AC:

371

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1141

2283

3424

4566

5707

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

310

620

930

1240

1550

<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:

0.155

Hom.:

4327

Bravo

AF:

0.221

Asia WGS

AF:

0.248

AC:

862

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Sep 21, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Apr 09, 2025

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiovascular phenotype

Benign:1

Feb 03, 2019

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.037

(source)

DANN

Benign

0.64

PhyloP100

-3.6

Mutation Taster

=285/15

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over