rs35168378

Positions:

chr16-870870-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_022773.4(LMF1):c.1091G>A(p.Arg364Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0268 in 1,608,236 control chromosomes in the GnomAD database, including 687 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.028 ( 60 hom., cov: 33)

Exomes 𝑓: 0.027 ( 627 hom. )

Consequence

LMF1
NM_022773.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 5.82

Variant links:

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 links:

LMF1 (HGNC:):

LMF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0055995286).

BP6

Variant 16-870870-C-T is Benign according to our data. Variant chr16-870870-C-T is described in ClinVar as [Benign]. Clinvar id is 978327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-870870-C-T is described in Lovd as [Likely_benign].

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMF1	NM_022773.4 linkuse as main transcript	c.1091G>A	p.Arg364Gln	missense_variant	8/11	ENST00000262301.16	NP_073610.2	Q96S06-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMF1	ENST00000262301.16 linkuse as main transcript	c.1091G>A	p.Arg364Gln	missense_variant	8/11	5	NM_022773.4	ENSP00000262301.12		Q96S06-1

Frequencies

GnomAD3 genomes

AF:

0.0281

AC:

4278

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0351

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0224

Gnomad ASJ

AF:

0.0352

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0306

Gnomad FIN

AF:

0.0189

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0283

Gnomad OTH

AF:

0.0321

GnomAD3 exomes

AF:

0.0245

AC:

5902

AN:

240702

Hom.:

112

AF XY:

0.0251

AC XY:

3310

AN XY:

131722

show subpopulations

Gnomad AFR exome

AF:

0.0355

Gnomad AMR exome

AF:

0.0155

Gnomad ASJ exome

AF:

0.0341

Gnomad EAS exome

AF:

0.000396

Gnomad SAS exome

AF:

0.0264

Gnomad FIN exome

AF:

0.0168

Gnomad NFE exome

AF:

0.0293

Gnomad OTH exome

AF:

0.0304

GnomAD4 exome

AF:

0.0266

AC:

38788

AN:

1455948

Hom.:

627

Cov.:

AF XY:

0.0270

AC XY:

19525

AN XY:

724404

show subpopulations

Gnomad4 AFR exome

AF:

0.0392

Gnomad4 AMR exome

AF:

0.0175

Gnomad4 ASJ exome

AF:

0.0334

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0281

Gnomad4 FIN exome

AF:

0.0194

Gnomad4 NFE exome

AF:

0.0274

Gnomad4 OTH exome

AF:

0.0285

GnomAD4 genome

AF:

0.0281

AC:

4282

AN:

152288

Hom.:

Cov.:

AF XY:

0.0280

AC XY:

2088

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0352

Gnomad4 AMR

AF:

0.0224

Gnomad4 ASJ

AF:

0.0352

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0308

Gnomad4 FIN

AF:

0.0189

Gnomad4 NFE

AF:

0.0283

Gnomad4 OTH

AF:

0.0318

Alfa

AF:

0.0278

Hom.:

Bravo

AF:

0.0285

TwinsUK

AF:

0.0270

AC:

100

ALSPAC

AF:

0.0257

AC:

ESP6500AA

AF:

0.0365

AC:

155

ESP6500EA

AF:

0.0251

AC:

213

ExAC

AF:

0.0255

AC:

3077

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 01, 2019	This variant is associated with the following publications: (PMID: 31619059, 30037590, 33111339) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	Jul 26, 2019	- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 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

0.19

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.089

T;.;.

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.61

T;T;T

MetaRNN

Benign

0.0056

T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.6

M;.;.

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-2.6

D;D;D

REVEL

Benign

0.18

Sift

Benign

0.080

T;T;T

Sift4G

Benign

0.25

T;T;T

Polyphen

0.98

D;.;.

Vest4

0.34

MPC

0.16

ClinPred

0.034

GERP RS

5.5

Varity_R

0.63

gMVP

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over