chr16-911054-C-T

Variant names:

• chr16-911054-C-T
• rs2277892
• NM_022773.4:c.540G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_022773.4(LMF1):​c.540G>A​(p.Thr180Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,611,352 control chromosomes in the GnomAD database, including 18,712 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (4241 hom., cov: 32)
  • Exomes 𝑓: 0.12 (14471 hom.)
• Consequence: LMF1 NM_022773.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -3.63
• Publications: 24 publications found

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 Gene-Disease associations (from GenCC):

• lipase deficiency, combined

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics

LOC124903619 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 16-911054-C-T is Benign according to our data. Variant chr16-911054-C-T is described in ClinVar as Benign. ClinVar VariationId is 1247993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.63 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022773.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMF1	NM_022773.4	MANE Select	c.540G>A	p.Thr180Thr	synonymous	Exon 4 of 11	NP_073610.2
	LMF1	NM_001352020.1		c.540G>A	p.Thr180Thr	synonymous	Exon 4 of 11	NP_001338949.1
	LMF1	NM_001352019.2		c.213G>A	p.Thr71Thr	synonymous	Exon 4 of 11	NP_001338948.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMF1	ENST00000262301.16	TSL:5 MANE Select	c.540G>A	p.Thr180Thr	synonymous	Exon 4 of 11	ENSP00000262301.12
	LMF1	ENST00000963976.1		c.540G>A	p.Thr180Thr	synonymous	Exon 4 of 12	ENSP00000634035.1
	LMF1	ENST00000570014.5	TSL:5	c.213G>A	p.Thr71Thr	synonymous	Exon 4 of 7	ENSP00000454672.1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30374 AN: 151912 Hom.: 4221 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.0549

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.177

GnomAD2 exomes AF: 0.168 AC: 41289 AN: 245772 AF XY: 0.162

Gnomad AFR exome AF: 0.380

Gnomad AMR exome AF: 0.288

Gnomad ASJ exome AF: 0.102

Gnomad EAS exome AF: 0.250

Gnomad FIN exome AF: 0.0567

Gnomad NFE exome AF: 0.103

Gnomad OTH exome AF: 0.144

GnomAD4 exome AF: 0.124 AC: 181604 AN: 1459324 Hom.: 14471 Cov.: 33 AF XY: 0.126 AC XY: 91474 AN XY: 725868

African (AFR) AF: 0.388 AC: 12960 AN: 33424

American (AMR) AF: 0.283 AC: 12547 AN: 44332

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 2835 AN: 26128

East Asian (EAS) AF: 0.224 AC: 8886 AN: 39592

South Asian (SAS) AF: 0.223 AC: 19152 AN: 86056

European-Finnish (FIN) AF: 0.0603 AC: 3174 AN: 52638

Middle Eastern (MID) AF: 0.107 AC: 617 AN: 5768

European-Non Finnish (NFE) AF: 0.102 AC: 113258 AN: 1111074

Other (OTH) AF: 0.136 AC: 8175 AN: 60312

GnomAD4 genome AF: 0.200 AC: 30440 AN: 152028 Hom.: 4241 Cov.: 32 AF XY: 0.199 AC XY: 14815 AN XY: 74328

African (AFR) AF: 0.377 AC: 15617 AN: 41402

American (AMR) AF: 0.240 AC: 3662 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 385 AN: 3468

East Asian (EAS) AF: 0.242 AC: 1251 AN: 5168

South Asian (SAS) AF: 0.234 AC: 1128 AN: 4814

European-Finnish (FIN) AF: 0.0549 AC: 582 AN: 10592

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7235 AN: 67994

Other (OTH) AF: 0.176 AC: 371 AN: 2112

Alfa AF: 0.155 Hom.: 4327

Bravo AF: 0.221

Asia WGS AF: 0.248 AC: 862 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Cardiovascular phenotype (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.037
DANN	Benign	0.64
PhyloP100		-3.6
Mutation Taster		=285/15	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2277892; hg19: chr16-961054; COSMIC: COSV51894861;