dbSNP rs192520307: LMF1:p.Arg351Gln (chr16-871187-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_022773.4(LMF1):c.1052G>A(p.Arg351Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00176 in 1,606,970 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0044 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 9 hom. )

Consequence

LMF1
NM_022773.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -4.73

Publications

8 publications found

Variant links:

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: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet

LMF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.004293412).

BP6

Variant 16-871187-C-T is Benign according to our data. Variant chr16-871187-C-T is described in ClinVar as Benign. ClinVar VariationId is 403041.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 = 0.0044 (670/152350) while in subpopulation AFR AF = 0.0115 (480/41578). AF 95% confidence interval is 0.0107. There are 7 homozygotes in GnomAd4. There are 312 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LMF1	NM_022773.4	MANE Select	c.1052G>A	p.Arg351Gln	missense	Exon 7 of 11	NP_073610.2	Q96S06-1
LMF1	NM_001352020.1		c.1052G>A	p.Arg351Gln	missense	Exon 7 of 11	NP_001338949.1
LMF1	NM_001352019.2		c.725G>A	p.Arg242Gln	missense	Exon 7 of 11	NP_001338948.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LMF1	ENST00000262301.16	TSL:5 MANE Select	c.1052G>A	p.Arg351Gln	missense	Exon 7 of 11	ENSP00000262301.12	Q96S06-1
LMF1	ENST00000963976.1		c.1052G>A	p.Arg351Gln	missense	Exon 7 of 12	ENSP00000634035.1
LMF1	ENST00000568897.5	TSL:5	c.401G>A	p.Arg134Gln	missense	Exon 6 of 10	ENSP00000458135.1	H3BVI4

Frequencies

GnomAD3 genomes

AF:

0.00438

AC:

667

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0115

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00497

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00125

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00224

AC:

534

AN:

238566

AF XY:

0.00183

show subpopulations

Gnomad AFR exome

AF:

0.0121

Gnomad AMR exome

AF:

0.00432

Gnomad ASJ exome

AF:

0.00217

Gnomad EAS exome

AF:

0.0000569

Gnomad FIN exome

AF:

0.0000481

Gnomad NFE exome

AF:

0.00128

Gnomad OTH exome

AF:

0.00379

GnomAD4 exome

AF:

0.00148

AC:

2156

AN:

1454620

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

1017

AN XY:

723000

show subpopulations

African (AFR)

AF:

0.0117

AC:

390

AN:

33390

American (AMR)

AF:

0.00420

AC:

185

AN:

44050

Ashkenazi Jewish (ASJ)

AF:

0.00197

AC:

AN:

25914

East Asian (EAS)

AF:

0.00

AC:

AN:

39538

South Asian (SAS)

AF:

0.00128

AC:

109

AN:

85148

European-Finnish (FIN)

AF:

0.0000193

AC:

AN:

51764

Middle Eastern (MID)

AF:

0.00727

AC:

AN:

5224

European-Non Finnish (NFE)

AF:

0.00112

AC:

1243

AN:

1109526

Other (OTH)

AF:

0.00231

AC:

139

AN:

60066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

124

248

373

497

621

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00440

AC:

670

AN:

152350

Hom.:

Cov.:

AF XY:

0.00419

AC XY:

312

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.0115

AC:

480

AN:

41578

American (AMR)

AF:

0.00496

AC:

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00145

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00125

AC:

AN:

68028

Other (OTH)

AF:

0.00426

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

103

138

172

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00203

Hom.:

Bravo

AF:

0.00546

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00966

AC:

ESP6500EA

AF:

0.00109

AC:

ExAC

AF:

0.00215

AC:

259

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

not specified (3)

Cardiovascular phenotype (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.0020

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.031

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.48

MetaRNN

Benign

0.0043

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.30

PhyloP100

-4.7

PrimateAI

Benign

0.25

PROVEAN

Benign

0.15

REVEL

Benign

0.012

Sift

Benign

0.75

Sift4G

Benign

0.59

Polyphen

0.0040

Vest4

0.052

MVP

0.25

MPC

0.020

ClinPred

0.0021

GERP RS

-9.5

Varity_R

0.016

gMVP

0.38

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over