16-854301-G-T

Position:

• chr16-854301-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.*231C>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 0.0358 in 686,486 control chromosomes in the GnomAD database, including 527 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.036 (91 hom., cov: 33)
  • Exomes 𝑓: 0.036 (436 hom.)
• Consequence: LMF1 NM_022773.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.795

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 16-854301-G-T is Benign according to our data. Variant chr16-854301-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1196522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMF1	NM_022773.4	c.*231C>A		3_prime_UTR_variant	11/11	ENST00000262301.16	NP_073610.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMF1	ENST00000262301.16	c.*231C>A		3_prime_UTR_variant	11/11	5	NM_022773.4	ENSP00000262301	P1
	ENST00000655150.1	n.632-6731G>T		intron_variant, non_coding_transcript_variant
LMF1	ENST00000543238.5	c.*231C>A		3_prime_UTR_variant	8/8	2		ENSP00000437418
LMF1	ENST00000545827.6	c.*1472C>A		3_prime_UTR_variant, NMD_transcript_variant	12/12	2		ENSP00000443820

Frequencies

GnomAD3 genomes AF: 0.0359 AC: 5461 AN: 152120 Hom.: 91 Cov.: 33

Gnomad AFR AF: 0.0363

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0264

Gnomad ASJ AF: 0.0404

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.0501

Gnomad FIN AF: 0.0310

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0388

Gnomad OTH AF: 0.0364

GnomAD3 exomes AF: 0.0342 AC: 4485 AN: 131324 Hom.: 114 AF XY: 0.0360 AC XY: 2577 AN XY: 71648

Gnomad AFR exome AF: 0.0387

Gnomad AMR exome AF: 0.0201

Gnomad ASJ exome AF: 0.0374

Gnomad EAS exome AF: 0.0106

Gnomad SAS exome AF: 0.0486

Gnomad FIN exome AF: 0.0281

Gnomad NFE exome AF: 0.0385

Gnomad OTH exome AF: 0.0397

GnomAD4 exome AF: 0.0358 AC: 19130 AN: 534248 Hom.: 436 Cov.: 3 AF XY: 0.0374 AC XY: 10823 AN XY: 289474

Gnomad4 AFR exome AF: 0.0415

Gnomad4 AMR exome AF: 0.0213

Gnomad4 ASJ exome AF: 0.0378

Gnomad4 EAS exome AF: 0.0102

Gnomad4 SAS exome AF: 0.0492

Gnomad4 FIN exome AF: 0.0299

Gnomad4 NFE exome AF: 0.0373

Gnomad4 OTH exome AF: 0.0356

GnomAD4 genome AF: 0.0359 AC: 5467 AN: 152238 Hom.: 91 Cov.: 33 AF XY: 0.0366 AC XY: 2725 AN XY: 74446

Gnomad4 AFR AF: 0.0363

Gnomad4 AMR AF: 0.0263

Gnomad4 ASJ AF: 0.0404

Gnomad4 EAS AF: 0.0110

Gnomad4 SAS AF: 0.0510

Gnomad4 FIN AF: 0.0310

Gnomad4 NFE AF: 0.0387

Gnomad4 OTH AF: 0.0360

Alfa AF: 0.0201 Hom.: 11

Bravo AF: 0.0348

Asia WGS AF: 0.0290 AC: 100 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 01, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.45
DANN	Benign	0.48

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: rs75476513; hg19: chr16-904301;