Genetic Variant LMF1:c.514+227G>A (chr16-934017-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_001352018.2(LMF1):c.89G>A(p.Arg30His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 1,493,264 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0098 ( 25 hom., cov: 33)

Exomes 𝑓: 0.00090 ( 19 hom. )

Consequence

LMF1
NM_001352018.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.66

Publications

0 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 links:

LMF1-AS1 (HGNC:50469): (LMF1 antisense RNA 1)

LMF1-AS1 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 (BayesDel_noAF=-0.93).

BP6

Variant 16-934017-C-T is Benign according to our data. Variant chr16-934017-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1186510.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 = 0.00979 (1491/152280) while in subpopulation AFR AF = 0.0341 (1415/41542). AF 95% confidence interval is 0.0326. There are 25 homozygotes in GnomAd4. There are 693 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 25 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352018.2. 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.514+227G>A		intron	N/A	NP_073610.2	Q96S06-1
LMF1	NM_001352018.2		c.89G>A	p.Arg30His	missense	Exon 4 of 12	NP_001338947.1
LMF1	NM_001352020.1		c.514+227G>A		intron	N/A	NP_001338949.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LMF1	ENST00000262301.16	TSL:5 MANE Select	c.514+227G>A	intron	N/A	ENSP00000262301.12	Q96S06-1
LMF1	ENST00000963976.1		c.514+227G>A	intron	N/A	ENSP00000634035.1
LMF1	ENST00000568897.5	TSL:5	c.-138+20336G>A	intron	N/A	ENSP00000458135.1	H3BVI4

Frequencies

GnomAD3 genomes

AF:

0.00979

AC:

1490

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0341

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00574

GnomAD2 exomes

AF:

0.00213

AC:

276

AN:

129486

AF XY:

0.00168

show subpopulations

Gnomad AFR exome

AF:

0.0343

Gnomad AMR exome

AF:

0.00209

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000208

Gnomad OTH exome

AF:

0.00124

GnomAD4 exome

AF:

0.000905

AC:

1213

AN:

1340984

Hom.:

Cov.:

AF XY:

0.000816

AC XY:

539

AN XY:

660586

show subpopulations

African (AFR)

AF:

0.0333

AC:

1015

AN:

30504

American (AMR)

AF:

0.00231

AC:

AN:

34252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24000

East Asian (EAS)

AF:

0.00

AC:

AN:

33180

South Asian (SAS)

AF:

0.0000898

AC:

AN:

77912

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29240

Middle Eastern (MID)

AF:

0.00102

AC:

AN:

3910

European-Non Finnish (NFE)

AF:

0.00000950

AC:

AN:

1052836

Other (OTH)

AF:

0.00178

AC:

AN:

55150

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

124

186

248

310

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<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:

0.00979

AC:

1491

AN:

152280

Hom.:

Cov.:

AF XY:

0.00931

AC XY:

693

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0341

AC:

1415

AN:

41542

American (AMR)

AF:

0.00372

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68026

Other (OTH)

AF:

0.00568

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

134

202

269

336

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.000680

Hom.:

Bravo

AF:

0.0111

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.83

(source)

DANN

Benign

0.49

PhyloP100

-1.7

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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