rs192520307

Positions:

chr16-871187-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.73

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:

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=0.004293412).

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. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMF1	NM_022773.4 linkuse as main transcript	c.1052G>A	p.Arg351Gln	missense_variant	7/11	ENST00000262301.16	NP_073610.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMF1	ENST00000262301.16 linkuse as main transcript	c.1052G>A	p.Arg351Gln	missense_variant	7/11	5	NM_022773.4	ENSP00000262301	P1	Q96S06-1

Frequencies

GnomAD3 genomes

AF:

0.00438

AC:

667

AN:

152232

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00183

AC XY:

238

AN XY:

130148

show subpopulations

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.:

Cov.:

AF XY:

0.00141

AC XY:

1017

AN XY:

723000

show subpopulations

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.:

Cov.:

AF XY:

0.00419

AC XY:

312

AN XY:

74490

show subpopulations

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.:

Bravo

AF:

0.00546

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00966

AC:

ESP6500EA

AF:

0.00109

AC:

ExAC

AF:

0.00215

AC:

259

Asia WGS

AF:

0.00318

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	Labcorp Genetics (formerly Invitae), Labcorp	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

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

LIST_S2

Benign

0.48

T;T;T

MetaRNN

Benign

0.0043

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.30

N;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.25

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

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

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