rs192520307

chr16-871187-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_022773.4(LMF1):c.1052G>A(p.Arg351Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00176 in 1,606,970 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0044 (7 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (9 hom.)
• Consequence: LMF1 NM_022773.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -4.73

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004293412).
• BP6: Variant 16-871187-C-T is Benign according to our data. Variant chr16-871187-C-T is described in ClinVar as [Benign]. Clinvar id is 403041.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-871187-C-T is described in Lovd as [Likely_benign]. Variant chr16-871187-C-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0044 (670/152350) while in subpopulation AFR AF= 0.0115 (480/41578). AF 95% confidence interval is 0.0107. There are 7 homozygotes in gnomad4. There are 312 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMF1	NM_022773.4	c.1052G>A	p.Arg351Gln	missense_variant	7/11	ENST00000262301.16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMF1	ENST00000262301.16	c.1052G>A	p.Arg351Gln	missense_variant	7/11	5	NM_022773.4	P1

Frequencies

GnomAD3 genomes AF: 0.00438 AC: 667 AN: 152232 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.0115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00497

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00125

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00224 AC: 534 AN: 238566 Hom.: 3 AF XY: 0.00183 AC XY: 238 AN XY: 130148

Gnomad AFR exome AF: 0.0121

Gnomad AMR exome AF: 0.00432

Gnomad ASJ exome AF: 0.00217

Gnomad EAS exome AF: 0.0000569

Gnomad SAS exome AF: 0.00116

Gnomad FIN exome AF: 0.0000481

Gnomad NFE exome AF: 0.00128

Gnomad OTH exome AF: 0.00379

GnomAD4 exome AF: 0.00148 AC: 2156 AN: 1454620 Hom.: 9 Cov.: 32 AF XY: 0.00141 AC XY: 1017 AN XY: 723000

Gnomad4 AFR exome AF: 0.0117

Gnomad4 AMR exome AF: 0.00420

Gnomad4 ASJ exome AF: 0.00197

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00128

Gnomad4 FIN exome AF: 0.0000193

Gnomad4 NFE exome AF: 0.00112

Gnomad4 OTH exome AF: 0.00231

GnomAD4 genome AF: 0.00440 AC: 670 AN: 152350 Hom.: 7 Cov.: 33 AF XY: 0.00419 AC XY: 312 AN XY: 74490

Gnomad4 AFR AF: 0.0115

Gnomad4 AMR AF: 0.00496

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00125

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00200 Hom.: 0

Bravo AF: 0.00546

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.00966 AC: 37

ESP6500EA AF: 0.00109 AC: 9

ExAC AF: 0.00215 AC: 259

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 18, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 10, 2020	This variant is associated with the following publications: (PMID: 31619059) -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Cardiovascular phenotype Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2019

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.0020
Dann	Benign	0.69
DEOGEN2	Benign	0.031	T;.;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.48	T;T;T
MetaRNN	Benign	0.0043	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.30	N;.;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.15	N;N;N
REVEL	Benign	0.012
Sift	Benign	0.75	T;T;T
Sift4G	Benign	0.59	T;T;T
Polyphen		0.0040	B;.;.
Vest4		0.052
MVP		0.25
MPC		0.020
ClinPred		0.0021	T
GERP RS		-9.5
Varity_R		0.016
gMVP		0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs192520307; hg19: chr16-921187;