Genetic Variant LMF1:p.Ala252Ala (chr16-879711-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_022773.4(LMF1):c.756G>A(p.Ala252Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,597,650 control chromosomes in the GnomAD database, including 13,159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1709 hom., cov: 33)

Exomes 𝑓: 0.12 ( 11450 hom. )

Consequence

LMF1
NM_022773.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.690

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 16-879711-C-T is Benign according to our data. Variant chr16-879711-C-T is described in ClinVar as [Benign]. Clinvar id is 1279701.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-879711-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.69 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMF1	NM_022773.4 link	c.756G>A	p.Ala252Ala	synonymous_variant	Exon 6 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.756G>A	p.Ala252Ala	synonymous_variant	Exon 6 of 11	5	NM_022773.4	ENSP00000262301.12		Q96S06-1

Frequencies

GnomAD3 genomes

AF:

0.138

AC:

20992

AN:

151884

Hom.:

1703

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.164

Gnomad AMR

AF:

0.0817

Gnomad ASJ

AF:

0.0744

Gnomad EAS

AF:

0.272

Gnomad SAS

AF:

0.133

Gnomad FIN

AF:

0.0661

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.115

GnomAD3 exomes

AF:

0.118

AC:

25762

AN:

218024

Hom.:

1863

AF XY:

0.118

AC XY:

13897

AN XY:

118192

show subpopulations

Gnomad AFR exome

AF:

0.209

Gnomad AMR exome

AF:

0.0538

Gnomad ASJ exome

AF:

0.0756

Gnomad EAS exome

AF:

0.261

Gnomad SAS exome

AF:

0.127

Gnomad FIN exome

AF:

0.0740

Gnomad NFE exome

AF:

0.115

Gnomad OTH exome

AF:

0.0975

GnomAD4 exome

AF:

0.119

AC:

172443

AN:

1445648

Hom.:

11450

Cov.:

AF XY:

0.119

AC XY:

85281

AN XY:

717368

show subpopulations

Gnomad4 AFR exome

AF:

0.216

Gnomad4 AMR exome

AF:

0.0571

Gnomad4 ASJ exome

AF:

0.0793

Gnomad4 EAS exome

AF:

0.282

Gnomad4 SAS exome

AF:

0.122

Gnomad4 FIN exome

AF:

0.0785

Gnomad4 NFE exome

AF:

0.116

Gnomad4 OTH exome

AF:

0.120

GnomAD4 genome

AF:

0.138

AC:

21029

AN:

152002

Hom.:

1709

Cov.:

AF XY:

0.136

AC XY:

10074

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.209

Gnomad4 AMR

AF:

0.0816

Gnomad4 ASJ

AF:

0.0744

Gnomad4 EAS

AF:

0.273

Gnomad4 SAS

AF:

0.132

Gnomad4 FIN

AF:

0.0661

Gnomad4 NFE

AF:

0.114

Gnomad4 OTH

AF:

0.115

Alfa

AF:

0.119

Hom.:

2313

Bravo

AF:

0.143

Asia WGS

AF:

0.258

AC:

895

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 04, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiovascular phenotype

Benign:1

Dec 11, 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

-0.38

CADD

Benign

8.6

DANN

Benign

0.80

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over