Genetic Variant LMF1:c.514+241C>G (chr16-934003-G-C) – 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_001352018.2(LMF1):c.103C>G(p.Arg35Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0834 in 1,480,490 control chromosomes in the GnomAD database, including 5,645 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.072 ( 457 hom., cov: 33)

Exomes 𝑓: 0.085 ( 5188 hom. )

Consequence

LMF1
NM_001352018.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.04

Publications

2 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 links:

LMF1-AS1 (HGNC:50469): (LMF1 antisense RNA 1)

LMF1-AS1 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=-1.06).

BP6

Variant 16-934003-G-C is Benign according to our data. Variant chr16-934003-G-C is described in ClinVar as Benign. ClinVar VariationId is 1271022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0895 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352018.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LMF1	NM_022773.4	MANE Select	c.514+241C>G		intron	N/A	NP_073610.2	Q96S06-1
LMF1	NM_001352018.2		c.103C>G	p.Arg35Gly	missense	Exon 4 of 12	NP_001338947.1
LMF1	NM_001352020.1		c.514+241C>G		intron	N/A	NP_001338949.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LMF1	ENST00000262301.16	TSL:5 MANE Select	c.514+241C>G	intron	N/A	ENSP00000262301.12	Q96S06-1
LMF1	ENST00000963976.1		c.514+241C>G	intron	N/A	ENSP00000634035.1
LMF1	ENST00000568897.5	TSL:5	c.-138+20350C>G	intron	N/A	ENSP00000458135.1	H3BVI4

Frequencies

GnomAD3 genomes

AF:

0.0725

AC:

11024

AN:

152146

Hom.:

456

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0544

Gnomad AMI

AF:

0.0396

Gnomad AMR

AF:

0.0477

Gnomad ASJ

AF:

0.0700

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0538

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0914

Gnomad OTH

AF:

0.0750

GnomAD2 exomes

AF:

0.0648

AC:

8340

AN:

128766

AF XY:

0.0654

show subpopulations

Gnomad AFR exome

AF:

0.0542

Gnomad AMR exome

AF:

0.0385

Gnomad ASJ exome

AF:

0.0684

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.0887

Gnomad OTH exome

AF:

0.0766

GnomAD4 exome

AF:

0.0847

AC:

112500

AN:

1328226

Hom.:

5188

Cov.:

AF XY:

0.0841

AC XY:

54993

AN XY:

653858

show subpopulations

African (AFR)

AF:

0.0525

AC:

1587

AN:

30250

American (AMR)

AF:

0.0406

AC:

1375

AN:

33840

Ashkenazi Jewish (ASJ)

AF:

0.0629

AC:

1485

AN:

23610

East Asian (EAS)

AF:

0.0000933

AC:

AN:

32168

South Asian (SAS)

AF:

0.0588

AC:

4573

AN:

77776

European-Finnish (FIN)

AF:

0.118

AC:

3297

AN:

27876

Middle Eastern (MID)

AF:

0.0796

AC:

303

AN:

3808

European-Non Finnish (NFE)

AF:

0.0916

AC:

95684

AN:

1044572

Other (OTH)

AF:

0.0772

AC:

4193

AN:

54326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

5338

10676

16014

21352

26690

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3584

7168

10752

14336

17920

<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:

0.0724

AC:

11030

AN:

152264

Hom.:

457

Cov.:

AF XY:

0.0718

AC XY:

5347

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0544

AC:

2261

AN:

41540

American (AMR)

AF:

0.0477

AC:

729

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0700

AC:

243

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5178

South Asian (SAS)

AF:

0.0537

AC:

259

AN:

4826

European-Finnish (FIN)

AF:

0.105

AC:

1113

AN:

10616

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0914

AC:

6217

AN:

68020

Other (OTH)

AF:

0.0747

AC:

158

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

534

1068

1602

2136

2670

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

130

260

390

520

650

<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:

0.0798

Hom.:

Bravo

AF:

0.0661

Asia WGS

AF:

0.0260

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

LMF1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.15

(source)

DANN

Benign

0.31

PhyloP100

-2.0

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over