16-854236-C-T

Position:

• chr16-854236-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_022773.4(LMF1):​c.*296G>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 0.00407 in 612,978 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (28 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (16 hom.)
• Consequence: LMF1 NM_022773.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.02

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=-0.89).
• BP6: Variant 16-854236-C-T is Benign according to our data. Variant chr16-854236-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1197360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0115 (1744/152248) while in subpopulation AFR AF= 0.0397 (1648/41548). AF 95% confidence interval is 0.0381. There are 28 homozygotes in gnomad4. There are 834 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMF1	NM_022773.4	c.*296G>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.*296G>A		3_prime_UTR_variant	11/11	5	NM_022773.4	ENSP00000262301	P1
	ENST00000655150.1	n.632-6796C>T		intron_variant, non_coding_transcript_variant
LMF1	ENST00000543238.5	c.*296G>A		3_prime_UTR_variant	8/8	2		ENSP00000437418
LMF1	ENST00000545827.6	c.*1537G>A		3_prime_UTR_variant, NMD_transcript_variant	12/12	2		ENSP00000443820

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1743 AN: 152130 Hom.: 28 Cov.: 33

Gnomad AFR AF: 0.0398

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00464

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00670

GnomAD3 exomes AF: 0.00261 AC: 341 AN: 130602 Hom.: 3 AF XY: 0.00199 AC XY: 142 AN XY: 71282

Gnomad AFR exome AF: 0.0435

Gnomad AMR exome AF: 0.00255

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000192

Gnomad SAS exome AF: 0.000179

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000401

Gnomad OTH exome AF: 0.00150

GnomAD4 exome AF: 0.00162 AC: 748 AN: 460730 Hom.: 16 Cov.: 0 AF XY: 0.00124 AC XY: 311 AN XY: 251176

Gnomad4 AFR exome AF: 0.0391

Gnomad4 AMR exome AF: 0.00281

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000124

Gnomad4 SAS exome AF: 0.000147

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000652

Gnomad4 OTH exome AF: 0.00329

GnomAD4 genome AF: 0.0115 AC: 1744 AN: 152248 Hom.: 28 Cov.: 33 AF XY: 0.0112 AC XY: 834 AN XY: 74450

Gnomad4 AFR AF: 0.0397

Gnomad4 AMR AF: 0.00464

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00663

Alfa AF: 0.00479 Hom.: 1

Bravo AF: 0.0127

Asia WGS AF: 0.000866 AC: 3 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	clinical testing	GeneDx	Apr 20, 2019	- -
Likely 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	-0.89
CADD	Benign	3.0
DANN	Benign	0.67

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: rs114890365; hg19: chr16-904236;