16-939721-C-T

Variant names:

• chr16-939721-C-T
• rs8062983
• NM_022773.4:c.504-5467G>A

Variant summary

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

The NM_022773.4(LMF1):​c.504-5467G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 152,072 control chromosomes in the GnomAD database, including 18,881 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 0.48 (18881 hom., cov: 33)
• Consequence: LMF1 NM_022773.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.922
• Publications: 7 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMF1	NM_022773.4	c.504-5467G>A		intron_variant	Intron 2 of 10	ENST00000262301.16	NP_073610.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMF1	ENST00000262301.16	c.504-5467G>A		intron_variant	Intron 2 of 10	5	NM_022773.4	ENSP00000262301.12

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72279 AN: 151954 Hom.: 18831 Cov.: 33

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.476 AC: 72388 AN: 152072 Hom.: 18881 Cov.: 33 AF XY: 0.473 AC XY: 35167 AN XY: 74342

African (AFR) AF: 0.694 AC: 28786 AN: 41486

American (AMR) AF: 0.470 AC: 7178 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1144 AN: 3468

East Asian (EAS) AF: 0.407 AC: 2104 AN: 5174

South Asian (SAS) AF: 0.591 AC: 2851 AN: 4820

European-Finnish (FIN) AF: 0.310 AC: 3275 AN: 10552

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.376 AC: 25547 AN: 67976

Other (OTH) AF: 0.459 AC: 971 AN: 2114

Alfa AF: 0.293 Hom.: 752

Bravo AF: 0.493

Asia WGS AF: 0.547 AC: 1901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.2
DANN	Benign	0.55
PhyloP100		-0.92
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: rs8062983; hg19: chr16-989721; COSMIC: COSV51895258;