rs4984948

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_022773.4(LMF1):c.1685C>G(p.Pro562Arg) variant causes a missense change. The variant allele was found at a frequency of 0.02 in 1,608,040 control chromosomes in the GnomAD database, including 1,477 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 225 hom., cov: 33)

Exomes 𝑓: 0.019 ( 1252 hom. )

Consequence

LMF1
NM_022773.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.50

Publications

25 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:

ENSG00000287855 (HGNC:):

ENSG00000287855 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017978847).

BP6

Variant 16-854551-G-C is Benign according to our data. Variant chr16-854551-G-C is described in ClinVar as Benign. ClinVar VariationId is 1277320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMF1	NM_022773.4 link	c.1685C>G	p.Pro562Arg	missense_variant	Exon 11 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.1685C>G	p.Pro562Arg	missense_variant	Exon 11 of 11	5	NM_022773.4	ENSP00000262301.12		Q96S06-1

Frequencies

GnomAD3 genomes

AF:

0.0261

AC:

3977

AN:

152166

Hom.:

222

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00799

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.127

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.140

Gnomad SAS

AF:

0.0524

Gnomad FIN

AF:

0.0130

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00713

Gnomad OTH

AF:

0.0292

GnomAD2 exomes

AF:

0.0468

AC:

11050

AN:

236352

AF XY:

0.0412

show subpopulations

Gnomad AFR exome

AF:

0.00605

Gnomad AMR exome

AF:

0.175

Gnomad ASJ exome

AF:

0.00747

Gnomad EAS exome

AF:

0.137

Gnomad FIN exome

AF:

0.0111

Gnomad NFE exome

AF:

0.00683

Gnomad OTH exome

AF:

0.0329

GnomAD4 exome

AF:

0.0193

AC:

28119

AN:

1455756

Hom.:

1252

Cov.:

AF XY:

0.0197

AC XY:

14250

AN XY:

724096

show subpopulations

African (AFR)

AF:

0.00667

AC:

223

AN:

33444

American (AMR)

AF:

0.168

AC:

7412

AN:

44084

Ashkenazi Jewish (ASJ)

AF:

0.00683

AC:

178

AN:

26046

East Asian (EAS)

AF:

0.129

AC:

5094

AN:

39560

South Asian (SAS)

AF:

0.0517

AC:

4430

AN:

85662

European-Finnish (FIN)

AF:

0.0106

AC:

529

AN:

49928

Middle Eastern (MID)

AF:

0.00486

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00807

AC:

8967

AN:

1111078

Other (OTH)

AF:

0.0209

AC:

1258

AN:

60192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

1451

2902

4352

5803

7254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

546

1092

1638

2184

2730

<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:

0.0262

AC:

3984

AN:

152284

Hom.:

225

Cov.:

AF XY:

0.0300

AC XY:

2231

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.00796

AC:

331

AN:

41570

American (AMR)

AF:

0.128

AC:

1958

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00778

AC:

AN:

3472

East Asian (EAS)

AF:

0.140

AC:

722

AN:

5160

South Asian (SAS)

AF:

0.0523

AC:

252

AN:

4820

European-Finnish (FIN)

AF:

0.0130

AC:

138

AN:

10630

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00713

AC:

485

AN:

68006

Other (OTH)

AF:

0.0294

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

187

375

562

750

937

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.00983

Hom.:

Bravo

AF:

0.0332

TwinsUK

AF:

0.00836

AC:

ALSPAC

AF:

0.00934

AC:

ESP6500AA

AF:

0.00615

AC:

ESP6500EA

AF:

0.00910

AC:

ExAC

AF:

0.0371

AC:

4454

Asia WGS

AF:

0.0760

AC:

264

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 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 17, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 27108409, 22239554, 25817768, 30420299) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

Mar 22, 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

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.27

T;.;.

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.54

T;T;T

MetaRNN

Benign

0.0018

T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.9

M;.;.

PhyloP100

4.5

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.8

D;D;D

REVEL

Benign

0.25

Sift

Benign

0.084

T;T;T

Sift4G

Benign

0.19

T;T;T

Polyphen

0.75

P;.;.

Vest4

0.19

MPC

0.10

ClinPred

0.032

GERP RS

4.4

Varity_R

0.30

gMVP

0.62

Mutation Taster

=89/11

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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