16-854358-G-T

Position:

• chr16-854358-G-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.*174C>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 0.00274 in 774,922 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0085 (28 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (8 hom.)
• Consequence: LMF1 NM_022773.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.07

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=-0.94).
• BP6: Variant 16-854358-G-T is Benign according to our data. Variant chr16-854358-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2446602.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00851 (1295/152254) while in subpopulation AFR AF= 0.0299 (1244/41554). AF 95% confidence interval is 0.0286. There are 28 homozygotes in gnomad4. There are 599 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.*174C>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.*174C>A		3_prime_UTR_variant	11/11	5	NM_022773.4	ENSP00000262301	P1
	ENST00000655150.1	n.632-6674G>T		intron_variant, non_coding_transcript_variant
LMF1	ENST00000543238.5	c.*174C>A		3_prime_UTR_variant	8/8	2		ENSP00000437418
LMF1	ENST00000545827.6	c.*1415C>A		3_prime_UTR_variant, NMD_transcript_variant	12/12	2		ENSP00000443820

Frequencies

GnomAD3 genomes AF: 0.00847 AC: 1289 AN: 152136 Hom.: 27 Cov.: 33

Gnomad AFR AF: 0.0299

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00527

GnomAD3 exomes AF: 0.00221 AC: 285 AN: 129182 Hom.: 1 AF XY: 0.00159 AC XY: 112 AN XY: 70398

Gnomad AFR exome AF: 0.0343

Gnomad AMR exome AF: 0.00172

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00106

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000990

Gnomad OTH exome AF: 0.000757

GnomAD4 exome AF: 0.00133 AC: 831 AN: 622668 Hom.: 8 Cov.: 8 AF XY: 0.00108 AC XY: 360 AN XY: 331890

Gnomad4 AFR exome AF: 0.0349

Gnomad4 AMR exome AF: 0.00228

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000621

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000412

Gnomad4 OTH exome AF: 0.00324

GnomAD4 genome AF: 0.00851 AC: 1295 AN: 152254 Hom.: 28 Cov.: 33 AF XY: 0.00804 AC XY: 599 AN XY: 74462

Gnomad4 AFR AF: 0.0299

Gnomad4 AMR AF: 0.00209

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00522

Alfa AF: 0.000517 Hom.: 0

Bravo AF: 0.0106

Asia WGS AF: 0.00549 AC: 19 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 21, 2019

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.36
DANN	Benign	0.37

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: rs78699640; hg19: chr16-904358;