rs2277892

chr16-911054-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.63

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 -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	UniProt
LMF1	NM_022773.4	c.540G>A	p.Thr180=	synonymous_variant	4/11	ENST00000262301.16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMF1	ENST00000262301.16	c.540G>A	p.Thr180=	synonymous_variant	4/11	5	NM_022773.4	P1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30374 AN: 151912 Hom.: 4221 Cov.: 32

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

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.: 33 AF XY: 0.126 AC XY: 91474 AN XY: 725868

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.: 32 AF XY: 0.199 AC XY: 14815 AN XY: 74328

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 21, 2018	- -

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

Other links and lift over

dbSNP: rs2277892; hg19: chr16-961054; COSMIC: COSV51894861;