Genetic Variant LMF1:c.514+2521C>T (chr16-931723-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001352017.2(LMF1):c.-219C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.032 in 1,287,190 control chromosomes in the GnomAD database, including 816 homozygotes. 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 0.023 ( 57 hom., cov: 33)

Exomes 𝑓: 0.033 ( 759 hom. )

Consequence

LMF1
NM_001352017.2 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.432

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0233 (3551/152302) while in subpopulation NFE AF= 0.0367 (2494/68006). AF 95% confidence interval is 0.0355. There are 57 homozygotes in gnomad4. There are 1624 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 57 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMF1	NM_022773.4 link	c.514+2521C>T		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+2521C>T		intron_variant	Intron 3 of 10	5	NM_022773.4	ENSP00000262301.12		Q96S06-1

Frequencies

GnomAD3 genomes

AF:

0.0233

AC:

3552

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00613

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0154

Gnomad ASJ

AF:

0.0966

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00765

Gnomad FIN

AF:

0.0132

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0367

Gnomad OTH

AF:

0.0215

GnomAD3 exomes

AF:

0.0267

AC:

3419

AN:

128054

Hom.:

AF XY:

0.0273

AC XY:

1915

AN XY:

70120

show subpopulations

Gnomad AFR exome

AF:

0.00575

Gnomad AMR exome

AF:

0.0134

Gnomad ASJ exome

AF:

0.105

Gnomad EAS exome

AF:

0.0000959

Gnomad SAS exome

AF:

0.00795

Gnomad FIN exome

AF:

0.0204

Gnomad NFE exome

AF:

0.0379

Gnomad OTH exome

AF:

0.0323

GnomAD4 exome

AF:

0.0332

AC:

37645

AN:

1134888

Hom.:

759

Cov.:

AF XY:

0.0328

AC XY:

18252

AN XY:

556704

show subpopulations

Gnomad4 AFR exome

AF:

0.00546

Gnomad4 AMR exome

AF:

0.0134

Gnomad4 ASJ exome

AF:

0.106

Gnomad4 EAS exome

AF:

0.0000779

Gnomad4 SAS exome

AF:

0.00958

Gnomad4 FIN exome

AF:

0.0207

Gnomad4 NFE exome

AF:

0.0359

Gnomad4 OTH exome

AF:

0.0319

GnomAD4 genome

AF:

0.0233

AC:

3551

AN:

152302

Hom.:

Cov.:

AF XY:

0.0218

AC XY:

1624

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00613

Gnomad4 AMR

AF:

0.0154

Gnomad4 ASJ

AF:

0.0966

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00724

Gnomad4 FIN

AF:

0.0132

Gnomad4 NFE

AF:

0.0367

Gnomad4 OTH

AF:

0.0213

Alfa

AF:

0.0335

Hom.:

Bravo

AF:

0.0229

Asia WGS

AF:

0.00606

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.1

DANN

Benign

0.61

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