Genetic Variant LMF1:c.514+2452G>A (chr16-931792-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001352017.2(LMF1):c.-288G>A variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.004 in 1,286,224 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0034 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0041 ( 13 hom. )

Consequence

LMF1
NM_001352017.2 splice_region

Scores

Splicing: ADA: 0.00002453

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -1.76

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 made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 16-931792-C-T is Benign according to our data. Variant chr16-931792-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2584630.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00336 (512/152312) while in subpopulation NFE AF= 0.00535 (364/68034). AF 95% confidence interval is 0.0049. There are 2 homozygotes in gnomad4. There are 226 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMF1	NM_022773.4 link	c.514+2452G>A		intron_variant	Intron 3 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.514+2452G>A		intron_variant	Intron 3 of 10	5	NM_022773.4	ENSP00000262301.12		Q96S06-1

Frequencies

GnomAD3 genomes

AF:

0.00337

AC:

513

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.00339

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00535

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00391

AC:

501

AN:

127986

Hom.:

AF XY:

0.00381

AC XY:

267

AN XY:

70072

show subpopulations

Gnomad AFR exome

AF:

0.000493

Gnomad AMR exome

AF:

0.00316

Gnomad ASJ exome

AF:

0.00729

Gnomad EAS exome

AF:

0.0000959

Gnomad SAS exome

AF:

0.00197

Gnomad FIN exome

AF:

0.00353

Gnomad NFE exome

AF:

0.00592

Gnomad OTH exome

AF:

0.00451

GnomAD4 exome

AF:

0.00409

AC:

4635

AN:

1133912

Hom.:

Cov.:

AF XY:

0.00411

AC XY:

2283

AN XY:

555976

show subpopulations

Gnomad4 AFR exome

AF:

0.000493

Gnomad4 AMR exome

AF:

0.00294

Gnomad4 ASJ exome

AF:

0.00672

Gnomad4 EAS exome

AF:

0.0000782

Gnomad4 SAS exome

AF:

0.00254

Gnomad4 FIN exome

AF:

0.00308

Gnomad4 NFE exome

AF:

0.00437

Gnomad4 OTH exome

AF:

0.00380

GnomAD4 genome

AF:

0.00336

AC:

512

AN:

152312

Hom.:

Cov.:

AF XY:

0.00303

AC XY:

226

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000577

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.00339

Gnomad4 NFE

AF:

0.00535

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00468

Hom.:

Bravo

AF:

0.00323

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Lipase deficiency, combined

Uncertain:1

Nov 15, 2022

New York Genome Center

Significance: Uncertain significance

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

DANN

Benign

0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000025

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.50

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.50

Position offset: -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