16-931792-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_022773.4(LMF1):​c.514+2452G>A variant causes a intron 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0034 ( 2 hom., cov: 33)
Exomes 𝑓: 0.0041 ( 13 hom. )

Consequence

LMF1
NM_022773.4 intron

Scores

2
Splicing: ADA: 0.00002453
2

Clinical Significance

Uncertain significance criteria provided, single submitter U: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 -9 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.96).
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. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LMF1NM_022773.4 linkuse as main transcriptc.514+2452G>A intron_variant ENST00000262301.16 NP_073610.2
LMF1-AS1NR_110945.1 linkuse as main transcriptn.136-1309C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LMF1ENST00000262301.16 linkuse as main transcriptc.514+2452G>A intron_variant 5 NM_022773.4 ENSP00000262301 P1Q96S06-1
LMF1-AS1ENST00000569574.1 linkuse as main transcriptn.96-1309C>T intron_variant, non_coding_transcript_variant 3

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: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Lipase deficiency, combined Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingNew York Genome CenterNov 15, 2022- -

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