rs2277893

chr16-911051-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.543G>A(p.Gly181=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 1,611,206 control chromosomes in the GnomAD database, including 45,350 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (8429 hom., cov: 32)
  • Exomes 𝑓: 0.21 (36921 hom.)
• Consequence: LMF1 NM_022773.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.07

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=-0.74).
• BP6: Variant 16-911051-C-T is Benign according to our data. Variant chr16-911051-C-T is described in ClinVar as [Benign]. Clinvar id is 1278135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-911051-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-3.07 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMF1	NM_022773.4	c.543G>A	p.Gly181=	synonymous_variant	4/11	ENST00000262301.16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMF1	ENST00000262301.16	c.543G>A	p.Gly181=	synonymous_variant	4/11	5	NM_022773.4	P1

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44956 AN: 151874 Hom.: 8400 Cov.: 32

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.278

GnomAD3 exomes AF: 0.263 AC: 64563 AN: 245852 Hom.: 10395 AF XY: 0.259 AC XY: 34594 AN XY: 133756

Gnomad AFR exome AF: 0.510

Gnomad AMR exome AF: 0.398

Gnomad ASJ exome AF: 0.148

Gnomad EAS exome AF: 0.317

Gnomad SAS exome AF: 0.424

Gnomad FIN exome AF: 0.139

Gnomad NFE exome AF: 0.171

Gnomad OTH exome AF: 0.232

GnomAD4 exome AF: 0.206 AC: 300436 AN: 1459214 Hom.: 36921 Cov.: 33 AF XY: 0.210 AC XY: 152746 AN XY: 725814

Gnomad4 AFR exome AF: 0.523

Gnomad4 AMR exome AF: 0.395

Gnomad4 ASJ exome AF: 0.154

Gnomad4 EAS exome AF: 0.292

Gnomad4 SAS exome AF: 0.417

Gnomad4 FIN exome AF: 0.138

Gnomad4 NFE exome AF: 0.173

Gnomad4 OTH exome AF: 0.226

GnomAD4 genome AF: 0.296 AC: 45022 AN: 151992 Hom.: 8429 Cov.: 32 AF XY: 0.297 AC XY: 22097 AN XY: 74296

Gnomad4 AFR AF: 0.506

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.276

Alfa AF: 0.224 Hom.: 2103

Bravo AF: 0.318

Asia WGS AF: 0.398 AC: 1383 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	GeneDx	Aug 30, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Cardiovascular phenotype Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2018

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	-0.74
Cadd	Benign	0.87
Dann	Benign	0.39

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: rs2277893; hg19: chr16-961051; COSMIC: COSV51894854;