16-939721-C-T

Position:

• chr16-939721-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022773.4(LMF1):​c.504-5467G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 152,072 control chromosomes in the GnomAD database, including 18,881 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (18881 hom., cov: 33)
• Consequence: LMF1 NM_022773.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.922

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMF1	NM_022773.4	c.504-5467G>A		intron_variant		ENST00000262301.16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMF1	ENST00000262301.16	c.504-5467G>A		intron_variant		5	NM_022773.4	P1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72279 AN: 151954 Hom.: 18831 Cov.: 33

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.461

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.476 AC: 72388 AN: 152072 Hom.: 18881 Cov.: 33 AF XY: 0.473 AC XY: 35167 AN XY: 74342

Gnomad4 AFR AF: 0.694

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.591

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.459

Alfa AF: 0.265 Hom.: 570

Bravo AF: 0.493

Asia WGS AF: 0.547 AC: 1901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.2
DANN	Benign	0.55

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: rs8062983; hg19: chr16-989721; COSMIC: COSV51895258;