rs2277893

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.543G>A(p.Gly181Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 1,611,206 control chromosomes in the GnomAD database, including 45,350 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 8429 hom., cov: 32)

Exomes 𝑓: 0.21 ( 36921 hom. )

Consequence

LMF1
NM_022773.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.07

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=-0.74).

BP6

Variant 16-911051-C-T is Benign according to our data. Variant chr16-911051-C-T is described in ClinVar as Benign. ClinVar VariationId is 1278135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.07 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMF1	NM_022773.4 link	c.543G>A	p.Gly181Gly	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.543G>A	p.Gly181Gly	synonymous_variant	Exon 4 of 11	5	NM_022773.4	ENSP00000262301.12		Q96S06-1

Frequencies

GnomAD3 genomes

AF:

0.296

AC:

44956

AN:

151874

Hom.:

8400

Cov.:

show subpopulations

Gnomad AFR

AF:

0.506

Gnomad AMI

AF:

0.365

Gnomad AMR

AF:

0.344

Gnomad ASJ

AF:

0.159

Gnomad EAS

AF:

0.307

Gnomad SAS

AF:

0.442

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.177

Gnomad OTH

AF:

0.278

GnomAD2 exomes

AF:

0.263

AC:

64563

AN:

245852

AF XY:

0.259

show subpopulations

Gnomad AFR exome

AF:

0.510

Gnomad AMR exome

AF:

0.398

Gnomad ASJ exome

AF:

0.148

Gnomad EAS exome

AF:

0.317

Gnomad FIN exome

AF:

0.139

Gnomad NFE exome

AF:

0.171

Gnomad OTH exome

AF:

0.232

GnomAD4 exome

AF:

0.206

AC:

300436

AN:

1459214

Hom.:

36921

Cov.:

AF XY:

0.210

AC XY:

152746

AN XY:

725814

show subpopulations

African (AFR)

AF:

0.523

AC:

17488

AN:

33420

American (AMR)

AF:

0.395

AC:

17511

AN:

44316

Ashkenazi Jewish (ASJ)

AF:

0.154

AC:

4012

AN:

26126

East Asian (EAS)

AF:

0.292

AC:

11562

AN:

39610

South Asian (SAS)

AF:

0.417

AC:

35880

AN:

86088

European-Finnish (FIN)

AF:

0.138

AC:

7262

AN:

52614

Middle Eastern (MID)

AF:

0.242

AC:

1394

AN:

5768

European-Non Finnish (NFE)

AF:

0.173

AC:

191689

AN:

1110972

Other (OTH)

AF:

0.226

AC:

13638

AN:

60300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

11596

23192

34787

46383

57979

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7184

14368

21552

28736

35920

<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:

0.296

AC:

45022

AN:

151992

Hom.:

8429

Cov.:

AF XY:

0.297

AC XY:

22097

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.506

AC:

20957

AN:

41392

American (AMR)

AF:

0.345

AC:

5272

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.159

AC:

552

AN:

3466

East Asian (EAS)

AF:

0.308

AC:

1590

AN:

5168

South Asian (SAS)

AF:

0.441

AC:

2127

AN:

4820

European-Finnish (FIN)

AF:

0.144

AC:

1523

AN:

10594

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.177

AC:

12013

AN:

67968

Other (OTH)

AF:

0.276

AC:

584

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1460

2920

4379

5839

7299

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

436

872

1308

1744

2180

<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:

0.228

Hom.:

2207

Bravo

AF:

0.318

Asia WGS

AF:

0.398

AC:

1383

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 30, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

Dec 03, 2018

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

-0.74

CADD

Benign

0.87

(source)

DANN

Benign

0.39

PhyloP100

-3.1

Mutation Taster

=286/14

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