16-854395-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_022773.4(LMF1):c.*137G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00208 in 914,578 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0074 (6 hom., cov: 33)
  • Exomes 𝑓: 0.0010 (7 hom.)
• Consequence: LMF1 NM_022773.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.22

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 16-854395-C-T is Benign according to our data. Variant chr16-854395-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1213201.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00742 (1129/152214) while in subpopulation AFR AF= 0.0248 (1029/41516). AF 95% confidence interval is 0.0235. There are 6 homozygotes in gnomad4. There are 522 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMF1	NM_022773.4	c.*137G>A		3_prime_UTR_variant	11/11	ENST00000262301.16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMF1	ENST00000262301.16	c.*137G>A		3_prime_UTR_variant	11/11	5	NM_022773.4	P1
	ENST00000655150.1	n.632-6637C>T		intron_variant, non_coding_transcript_variant
LMF1	ENST00000543238.5	c.*137G>A		3_prime_UTR_variant	8/8	2
LMF1	ENST00000545827.6	c.*1378G>A		3_prime_UTR_variant, NMD_transcript_variant	12/12	2

Frequencies

GnomAD3 genomes AF: 0.00742 AC: 1128 AN: 152096 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.0248

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00320

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.00479

GnomAD3 exomes AF: 0.00187 AC: 225 AN: 120566 Hom.: 0 AF XY: 0.00138 AC XY: 90 AN XY: 65248

Gnomad AFR exome AF: 0.0245

Gnomad AMR exome AF: 0.00165

Gnomad ASJ exome AF: 0.000750

Gnomad EAS exome AF: 0.0000980

Gnomad SAS exome AF: 0.0000517

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000504

Gnomad OTH exome AF: 0.00109

GnomAD4 exome AF: 0.00101 AC: 769 AN: 762364 Hom.: 7 Cov.: 10 AF XY: 0.000839 AC XY: 332 AN XY: 395836

Gnomad4 AFR exome AF: 0.0229

Gnomad4 AMR exome AF: 0.00160

Gnomad4 ASJ exome AF: 0.000598

Gnomad4 EAS exome AF: 0.0000305

Gnomad4 SAS exome AF: 0.0000939

Gnomad4 FIN exome AF: 0.0000306

Gnomad4 NFE exome AF: 0.000344

Gnomad4 OTH exome AF: 0.00200

GnomAD4 genome AF: 0.00742 AC: 1129 AN: 152214 Hom.: 6 Cov.: 33 AF XY: 0.00701 AC XY: 522 AN XY: 74430

Gnomad4 AFR AF: 0.0248

Gnomad4 AMR AF: 0.00320

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000529

Gnomad4 OTH AF: 0.00474

Alfa AF: 0.00373 Hom.: 0

Bravo AF: 0.00788

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	2.1
Dann	Benign	0.49

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: rs147193806; hg19: chr16-904395;