rs4984982

Variant names:

• chr16-920598-C-A
• rs4984982
• NM_022773.4:c.515-9519G>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.515-9519G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 152,090 control chromosomes in the GnomAD database, including 16,339 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 (16339 hom., cov: 33)
• Consequence: LMF1 NM_022773.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770
• Publications: 14 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.668 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.515-9519G>T		intron	N/A	NP_073610.2
	LMF1	NM_001352020.1		c.515-9519G>T		intron	N/A	NP_001338949.1
	LMF1	NM_001352019.2		c.188-9519G>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.515-9519G>T		intron	N/A	ENSP00000262301.12
	LMF1	ENST00000568897.5	TSL:5	c.-137-9519G>T		intron	N/A	ENSP00000458135.1
	LMF1	ENST00000543238.5	TSL:2	c.-48-27526G>T		intron	N/A	ENSP00000437418.1

Frequencies

GnomAD3 genomes AF: 0.434 AC: 66017 AN: 151972 Hom.: 16311 Cov.: 33

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.414

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

GnomAD4 genome AF: 0.435 AC: 66101 AN: 152090 Hom.: 16339 Cov.: 33 AF XY: 0.429 AC XY: 31896 AN XY: 74360

African (AFR) AF: 0.674 AC: 27960 AN: 41468

American (AMR) AF: 0.444 AC: 6792 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 964 AN: 3468

East Asian (EAS) AF: 0.299 AC: 1546 AN: 5164

South Asian (SAS) AF: 0.459 AC: 2219 AN: 4830

European-Finnish (FIN) AF: 0.242 AC: 2560 AN: 10578

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22682 AN: 67974

Other (OTH) AF: 0.411 AC: 868 AN: 2112

Alfa AF: 0.363 Hom.: 6289

Bravo AF: 0.458

Asia WGS AF: 0.401 AC: 1394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.36
PhyloP100		0.077
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: rs4984982; hg19: chr16-970598;