16-931792-C-T
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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
NM_022773.4 intron
Scores
2
Splicing: ADA: 0.00002453
2
Clinical Significance
Conservation
PhyloP100: -1.76
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]
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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 |
---|---|---|---|---|---|---|---|---|
LMF1 | NM_022773.4 | c.514+2452G>A | intron_variant | ENST00000262301.16 | NP_073610.2 | |||
LMF1-AS1 | NR_110945.1 | n.136-1309C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LMF1 | ENST00000262301.16 | c.514+2452G>A | intron_variant | 5 | NM_022773.4 | ENSP00000262301 | P1 | |||
LMF1-AS1 | ENST00000569574.1 | n.96-1309C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.00337 AC: 513AN: 152194Hom.: 2 Cov.: 33
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GnomAD3 exomes AF: 0.00391 AC: 501AN: 127986Hom.: 0 AF XY: 0.00381 AC XY: 267AN XY: 70072
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GnomAD4 exome AF: 0.00409 AC: 4635AN: 1133912Hom.: 13 Cov.: 31 AF XY: 0.00411 AC XY: 2283AN XY: 555976
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GnomAD4 genome AF: 0.00336 AC: 512AN: 152312Hom.: 2 Cov.: 33 AF XY: 0.00303 AC XY: 226AN XY: 74486
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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 submitter | clinical testing | New York Genome Center | Nov 15, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at