Genetic Variant LMF1:c.194-28T>C (chr16-954694-A-G) – ACMG Classification: Benign (-20 pts)

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.194-28T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 1,559,114 control chromosomes in the GnomAD database, including 138,846 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 20609 hom., cov: 34)

Exomes 𝑓: 0.40 ( 118237 hom. )

Consequence

LMF1
NM_022773.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.15

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:

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 (BayesDel_noAF=-0.92).

BP6

Variant 16-954694-A-G is Benign according to our data. Variant chr16-954694-A-G is described in ClinVar as Benign. ClinVar VariationId is 1275485.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMF1	NM_022773.4 link	c.194-28T>C		intron_variant	Intron 1 of 10	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.194-28T>C		intron_variant	Intron 1 of 10	5	NM_022773.4	ENSP00000262301.12		Q96S06-1

Frequencies

GnomAD3 genomes

AF:

0.493

AC:

74904

AN:

152052

Hom.:

20560

Cov.:

show subpopulations

Gnomad AFR

AF:

0.742

Gnomad AMI

AF:

0.477

Gnomad AMR

AF:

0.477

Gnomad ASJ

AF:

0.333

Gnomad EAS

AF:

0.397

Gnomad SAS

AF:

0.595

Gnomad FIN

AF:

0.309

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.382

Gnomad OTH

AF:

0.469

GnomAD2 exomes

AF:

0.444

AC:

90811

AN:

204676

AF XY:

0.438

show subpopulations

Gnomad AFR exome

AF:

0.752

Gnomad AMR exome

AF:

0.498

Gnomad ASJ exome

AF:

0.322

Gnomad EAS exome

AF:

0.402

Gnomad FIN exome

AF:

0.324

Gnomad NFE exome

AF:

0.380

Gnomad OTH exome

AF:

0.418

GnomAD4 exome

AF:

0.402

AC:

565134

AN:

1406944

Hom.:

118237

Cov.:

AF XY:

0.405

AC XY:

280881

AN XY:

693888

show subpopulations

African (AFR)

AF:

0.765

AC:

24573

AN:

32140

American (AMR)

AF:

0.499

AC:

20081

AN:

40230

Ashkenazi Jewish (ASJ)

AF:

0.319

AC:

7243

AN:

22736

East Asian (EAS)

AF:

0.380

AC:

14925

AN:

39266

South Asian (SAS)

AF:

0.574

AC:

44366

AN:

77270

European-Finnish (FIN)

AF:

0.327

AC:

15091

AN:

46216

Middle Eastern (MID)

AF:

0.406

AC:

2224

AN:

5482

European-Non Finnish (NFE)

AF:

0.380

AC:

412616

AN:

1085416

Other (OTH)

AF:

0.413

AC:

24015

AN:

58188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

17342

34685

52027

69370

86712

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13452

26904

40356

53808

67260

<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:

0.493

AC:

75011

AN:

152170

Hom.:

20609

Cov.:

AF XY:

0.489

AC XY:

36394

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.742

AC:

30818

AN:

41516

American (AMR)

AF:

0.478

AC:

7306

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.333

AC:

1154

AN:

3462

East Asian (EAS)

AF:

0.397

AC:

2056

AN:

5180

South Asian (SAS)

AF:

0.594

AC:

2863

AN:

4818

European-Finnish (FIN)

AF:

0.309

AC:

3279

AN:

10598

Middle Eastern (MID)

AF:

0.357

AC:

105

AN:

294

European-Non Finnish (NFE)

AF:

0.383

AC:

26008

AN:

67992

Other (OTH)

AF:

0.468

AC:

988

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1805

3610

5416

7221

9026

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

650

1300

1950

2600

3250

<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:

0.423

Hom.:

35420

Bravo

AF:

0.512

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 16, 2019

GeneDx

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.0060

(source)

DANN

Benign

0.22

PhyloP100

-3.1

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over