Variant rs2277892 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_022773.4(LMF1):c.540G>A(p.Thr180=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,611,352 control chromosomes in the GnomAD database, including 18,712 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 4241 hom., cov: 32)

Exomes 𝑓: 0.12 ( 14471 hom. )

Consequence

LMF1
NM_022773.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.63

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 16-911054-C-T is Benign according to our data. Variant chr16-911054-C-T is described in ClinVar as [Benign]. Clinvar id is 1247993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-911054-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.63 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.372 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.540G>A	p.Thr180=	synonymous_variant	4/11	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.540G>A	p.Thr180=	synonymous_variant	4/11	5	NM_022773.4	ENSP00000262301	P1	Q96S06-1

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30374

AN:

151912

Hom.:

4221

Cov.:

show subpopulations

Gnomad AFR

AF:

0.377

Gnomad AMI

AF:

0.202

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.242

Gnomad SAS

AF:

0.234

Gnomad FIN

AF:

0.0549

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.177

GnomAD3 exomes

AF:

0.168

AC:

41289

AN:

245772

Hom.:

4498

AF XY:

0.162

AC XY:

21604

AN XY:

133694

show subpopulations

Gnomad AFR exome

AF:

0.380

Gnomad AMR exome

AF:

0.288

Gnomad ASJ exome

AF:

0.102

Gnomad EAS exome

AF:

0.250

Gnomad SAS exome

AF:

0.223

Gnomad FIN exome

AF:

0.0567

Gnomad NFE exome

AF:

0.103

Gnomad OTH exome

AF:

0.144

GnomAD4 exome

AF:

0.124

AC:

181604

AN:

1459324

Hom.:

14471

Cov.:

AF XY:

0.126

AC XY:

91474

AN XY:

725868

show subpopulations

Gnomad4 AFR exome

AF:

0.388

Gnomad4 AMR exome

AF:

0.283

Gnomad4 ASJ exome

AF:

0.109

Gnomad4 EAS exome

AF:

0.224

Gnomad4 SAS exome

AF:

0.223

Gnomad4 FIN exome

AF:

0.0603

Gnomad4 NFE exome

AF:

0.102

Gnomad4 OTH exome

AF:

0.136

GnomAD4 genome

AF:

0.200

AC:

30440

AN:

152028

Hom.:

4241

Cov.:

AF XY:

0.199

AC XY:

14815

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.377

Gnomad4 AMR

AF:

0.240

Gnomad4 ASJ

AF:

0.111

Gnomad4 EAS

AF:

0.242

Gnomad4 SAS

AF:

0.234

Gnomad4 FIN

AF:

0.0549

Gnomad4 NFE

AF:

0.106

Gnomad4 OTH

AF:

0.176

Alfa

AF:

0.133

Hom.:

2325

Bravo

AF:

0.221

Asia WGS

AF:

0.248

AC:

862

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 21, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 03, 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

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.037

DANN

Benign

0.64

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