Genetic Variant LMF1:c.-135+10144G>C (chr16-971001-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001352019.2(LMF1):c.-135+10144G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000019 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0000017 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LMF1
NM_001352019.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00

Publications

7 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:

ENSG00000292433 (HGNC:):

ENSG00000292433 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352019.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
LMF1	NM_001352019.2	c.-135+10144G>C	intron	N/A	NP_001338948.1
LMF1	NM_001352018.2	c.-362+10144G>C	intron	N/A	NP_001338947.1
LMF1	NM_001352017.2	c.-611+10144G>C	intron	N/A	NP_001338946.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
LMF1	ENST00000570014.5	TSL:5	c.-135+10144G>C	intron	N/A	ENSP00000454672.1
LMF1	ENST00000545827.6	TSL:2	n.-135+10144G>C	intron	N/A	ENSP00000443820.2
LMF1	ENST00000262301.16	TSL:5 MANE Select	c.-21G>C	upstream_gene	N/A	ENSP00000262301.12

Frequencies

GnomAD3 genomes

AF:

0.0000187

AC:

AN:

53386

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000344

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000171

AC:

AN:

585324

Hom.:

Cov.:

AF XY:

0.00000350

AC XY:

AN XY:

285450

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

5538

American (AMR)

AF:

0.00

AC:

AN:

11008

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11104

East Asian (EAS)

AF:

0.00

AC:

AN:

13790

South Asian (SAS)

AF:

0.00

AC:

AN:

21412

European-Finnish (FIN)

AF:

0.00

AC:

AN:

18368

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1870

European-Non Finnish (NFE)

AF:

0.00000209

AC:

AN:

478700

Other (OTH)

AF:

0.00

AC:

AN:

23534

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000187

AC:

AN:

53386

Hom.:

Cov.:

AF XY:

0.0000378

AC XY:

AN XY:

26446

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

7610

American (AMR)

AF:

0.00

AC:

AN:

5388

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1864

East Asian (EAS)

AF:

0.00

AC:

AN:

1962

South Asian (SAS)

AF:

0.00

AC:

AN:

1344

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4888

Middle Eastern (MID)

AF:

0.00

AC:

AN:

156

European-Non Finnish (NFE)

AF:

0.0000344

AC:

AN:

29090

Other (OTH)

AF:

0.00

AC:

AN:

860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

3.8

(source)

DANN

Benign

0.19

PhyloP100

0.0

PromoterAI

0.024

Neutral

(source)

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over