16-870675-G-C

Variant names:

• chr16-870675-G-C
• rs13329717
• NM_022773.4:c.1232+54C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022773.4(LMF1):​c.1232+54C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0418 in 1,596,540 control chromosomes in the GnomAD database, including 2,362 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.075 (731 hom., cov: 33)
  • Exomes 𝑓: 0.038 (1631 hom.)
• Consequence: LMF1 NM_022773.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.230
• Publications: 4 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-870675-G-C is Benign according to our data. Variant chr16-870675-G-C is described in ClinVar as Benign. ClinVar VariationId is 1231465.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.175 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMF1	NM_022773.4	MANE Select	c.1232+54C>G		intron	N/A	NP_073610.2
	LMF1	NM_001352020.1		c.1232+54C>G		intron	N/A	NP_001338949.1
	LMF1	NM_001352019.2		c.905+54C>G		intron	N/A	NP_001338948.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMF1	ENST00000262301.16	TSL:5 MANE Select	c.1232+54C>G		intron	N/A	ENSP00000262301.12
	LMF1	ENST00000568897.5	TSL:5	c.581+54C>G		intron	N/A	ENSP00000458135.1
	LMF1	ENST00000543238.5	TSL:2	c.521+54C>G		intron	N/A	ENSP00000437418.1

Frequencies

GnomAD3 genomes AF: 0.0746 AC: 11356 AN: 152156 Hom.: 732 Cov.: 33

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0450

Gnomad ASJ AF: 0.0352

Gnomad EAS AF: 0.00732

Gnomad SAS AF: 0.0366

Gnomad FIN AF: 0.0238

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0364

Gnomad OTH AF: 0.0688

GnomAD4 exome AF: 0.0383 AC: 55377 AN: 1444266 Hom.: 1631 AF XY: 0.0382 AC XY: 27447 AN XY: 719366

African (AFR) AF: 0.188 AC: 6235 AN: 33160

American (AMR) AF: 0.0283 AC: 1264 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.0338 AC: 879 AN: 25986

East Asian (EAS) AF: 0.00686 AC: 272 AN: 39632

South Asian (SAS) AF: 0.0348 AC: 2984 AN: 85802

European-Finnish (FIN) AF: 0.0245 AC: 1205 AN: 49218

Middle Eastern (MID) AF: 0.0768 AC: 440 AN: 5726

European-Non Finnish (NFE) AF: 0.0359 AC: 39488 AN: 1100224

Other (OTH) AF: 0.0436 AC: 2610 AN: 59860

GnomAD4 genome AF: 0.0746 AC: 11366 AN: 152274 Hom.: 731 Cov.: 33 AF XY: 0.0737 AC XY: 5484 AN XY: 74456

African (AFR) AF: 0.179 AC: 7423 AN: 41538

American (AMR) AF: 0.0450 AC: 688 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0352 AC: 122 AN: 3470

East Asian (EAS) AF: 0.00734 AC: 38 AN: 5180

South Asian (SAS) AF: 0.0369 AC: 178 AN: 4830

European-Finnish (FIN) AF: 0.0238 AC: 253 AN: 10626

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0364 AC: 2473 AN: 68010

Other (OTH) AF: 0.0681 AC: 144 AN: 2114

Alfa AF: 0.0158 Hom.: 6

Bravo AF: 0.0811

Asia WGS AF: 0.0300 AC: 103 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Sep 21, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.0
DANN	Benign	0.73
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs13329717; hg19: chr16-920675;