NM_022773.4:c.504-1463C>T

Variant names:

• chr16-935717-G-A
• rs1544799
• NM_022773.4:c.504-1463C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022773.4(LMF1):​c.504-1463C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 152,142 control chromosomes in the GnomAD database, including 16,604 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 0.43 (16604 hom., cov: 34)
• Consequence: LMF1 NM_022773.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• lipase deficiency, combined

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022773.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMF1	NM_022773.4	MANE Select	c.504-1463C>T		intron	N/A	NP_073610.2
	LMF1	NM_001352020.1		c.504-1463C>T		intron	N/A	NP_001338949.1
	LMF1	NM_001352019.2		c.177-1463C>T		intron	N/A	NP_001338948.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMF1	ENST00000262301.16	TSL:5 MANE Select	c.504-1463C>T		intron	N/A	ENSP00000262301.12
	LMF1	ENST00000568897.5	TSL:5	c.-138+18636C>T		intron	N/A	ENSP00000458135.1
	LMF1	ENST00000543238.5	TSL:2	c.-49+35071C>T		intron	N/A	ENSP00000437418.1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 65030 AN: 152024 Hom.: 16554 Cov.: 34

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.401

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.428 AC: 65137 AN: 152142 Hom.: 16604 Cov.: 34 AF XY: 0.426 AC XY: 31699 AN XY: 74378

African (AFR) AF: 0.709 AC: 29422 AN: 41498

American (AMR) AF: 0.428 AC: 6541 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 906 AN: 3468

East Asian (EAS) AF: 0.412 AC: 2133 AN: 5180

South Asian (SAS) AF: 0.538 AC: 2596 AN: 4822

European-Finnish (FIN) AF: 0.242 AC: 2563 AN: 10574

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19647 AN: 67996

Other (OTH) AF: 0.398 AC: 843 AN: 2116

Alfa AF: 0.388 Hom.: 4724

Bravo AF: 0.451

Asia WGS AF: 0.523 AC: 1818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.6
DANN	Benign	0.59
PhyloP100		-0.083
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1544799; hg19: chr16-985717;