chr16-931792-C-T

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

2
Splicing: ADA: 0.00002453
2

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

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
LMF1NM_022773.4 linkc.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
LMF1ENST00000262301.16 linkc.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.:
2
Cov.:
33
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.:
0
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.:
13
Cov.:
31
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.:
2
Cov.:
33
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.:
0
Bravo
AF:
0.00323
Asia WGS
AF:
0.000577
AC:
2
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
19
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.

Other links and lift over

dbSNP: rs559176411; hg19: chr16-981792; API