rs13329717

Positions:

• chr16-870675-G-C
• chr16-870675-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022773.4(LMF1):​c.1232+54C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0418 in 1,596,540 control chromosomes in the GnomAD database, including 2,362 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.075 (731 hom., cov: 33)
  • Exomes 𝑓: 0.038 (1631 hom.)
• Consequence: LMF1 NM_022773.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.230

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-870675-G-C is Benign according to our data. Variant chr16-870675-G-C is described in ClinVar as [Benign]. Clinvar id is 1231465.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-870675-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMF1	NM_022773.4	c.1232+54C>G		intron_variant		ENST00000262301.16	NP_073610.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMF1	ENST00000262301.16	c.1232+54C>G		intron_variant		5	NM_022773.4	ENSP00000262301	P1

Frequencies

GnomAD3 genomes AF: 0.0746 AC: 11356 AN: 152156 Hom.: 732 Cov.: 33

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0450

Gnomad ASJ AF: 0.0352

Gnomad EAS AF: 0.00732

Gnomad SAS AF: 0.0366

Gnomad FIN AF: 0.0238

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0364

Gnomad OTH AF: 0.0688

GnomAD4 exome AF: 0.0383 AC: 55377 AN: 1444266 Hom.: 1631 AF XY: 0.0382 AC XY: 27447 AN XY: 719366

Gnomad4 AFR exome AF: 0.188

Gnomad4 AMR exome AF: 0.0283

Gnomad4 ASJ exome AF: 0.0338

Gnomad4 EAS exome AF: 0.00686

Gnomad4 SAS exome AF: 0.0348

Gnomad4 FIN exome AF: 0.0245

Gnomad4 NFE exome AF: 0.0359

Gnomad4 OTH exome AF: 0.0436

GnomAD4 genome AF: 0.0746 AC: 11366 AN: 152274 Hom.: 731 Cov.: 33 AF XY: 0.0737 AC XY: 5484 AN XY: 74456

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.0450

Gnomad4 ASJ AF: 0.0352

Gnomad4 EAS AF: 0.00734

Gnomad4 SAS AF: 0.0369

Gnomad4 FIN AF: 0.0238

Gnomad4 NFE AF: 0.0364

Gnomad4 OTH AF: 0.0681

Alfa AF: 0.0158 Hom.: 6

Bravo AF: 0.0811

Asia WGS AF: 0.0300 AC: 103 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 21, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.0
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs13329717; hg19: chr16-920675;