16-934444-G-A

Position:

• chr16-934444-G-A

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.504-190C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0759 in 639,318 control chromosomes in the GnomAD database, including 2,143 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.072 (456 hom., cov: 33)
  • Exomes 𝑓: 0.077 (1687 hom.)
• Consequence: LMF1 NM_022773.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.484

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-AS1 (HGNC:50469): (LMF1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-934444-G-A is Benign according to our data. Variant chr16-934444-G-A is described in ClinVar as [Benign]. Clinvar id is 1235310.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-934444-G-A is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMF1	NM_022773.4	c.504-190C>T		intron_variant		ENST00000262301.16	NP_073610.2
LMF1-AS1	NR_110945.1	n.1397G>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMF1	ENST00000262301.16	c.504-190C>T		intron_variant		5	NM_022773.4	ENSP00000262301	P1
LMF1-AS1	ENST00000569574.1	n.1357G>A		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes AF: 0.0722 AC: 10980 AN: 152156 Hom.: 455 Cov.: 33

Gnomad AFR AF: 0.0541

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0476

Gnomad ASJ AF: 0.0700

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0528

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0911

Gnomad OTH AF: 0.0740

GnomAD4 exome AF: 0.0770 AC: 37521 AN: 487044 Hom.: 1687 Cov.: 6 AF XY: 0.0767 AC XY: 19811 AN XY: 258130

Gnomad4 AFR exome AF: 0.0550

Gnomad4 AMR exome AF: 0.0482

Gnomad4 ASJ exome AF: 0.0613

Gnomad4 EAS exome AF: 0.0000324

Gnomad4 SAS exome AF: 0.0584

Gnomad4 FIN exome AF: 0.117

Gnomad4 NFE exome AF: 0.0879

Gnomad4 OTH exome AF: 0.0754

GnomAD4 genome AF: 0.0721 AC: 10983 AN: 152274 Hom.: 456 Cov.: 33 AF XY: 0.0715 AC XY: 5324 AN XY: 74434

Gnomad4 AFR AF: 0.0540

Gnomad4 AMR AF: 0.0476

Gnomad4 ASJ AF: 0.0700

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0527

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.0911

Gnomad4 OTH AF: 0.0737

Alfa AF: 0.0840 Hom.: 90

Bravo AF: 0.0658

Asia WGS AF: 0.0250 AC: 91 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.77

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: rs73483809; hg19: chr16-984444;