Genetic Variant NM_001352019.2:c.-135+10144G>T (chr16-971001-C-A) – 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_001352019.2(LMF1):c.-135+10144G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00075 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0075 ( 164 hom. )

Consequence

LMF1
NM_001352019.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.00

Publications

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

LMF1 links:

ENSG00000292433 (HGNC:):

ENSG00000292433 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=-0.75).

BP6

Variant 16-971001-C-A is Benign according to our data. Variant chr16-971001-C-A is described in ClinVar as Benign. ClinVar VariationId is 1242679.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 = 0.000749 (40/53398) while in subpopulation AFR AF = 0.00223 (17/7620). AF 95% confidence interval is 0.00142. There are 0 homozygotes in GnomAd4. There are 18 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 164 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMF1	NM_022773.4 link	c.-21G>T		upstream_gene_variant		ENST00000262301.16	NP_073610.2	Q96S06-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMF1	ENST00000262301.16 link	c.-21G>T		upstream_gene_variant		5	NM_022773.4	ENSP00000262301.12		Q96S06-1

Frequencies

GnomAD3 genomes

AF:

0.000749

AC:

AN:

53384

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00223

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000742

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000744

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000619

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0761

AC:

5608

AN:

73662

AF XY:

0.0733

show subpopulations

Gnomad AFR exome

AF:

0.114

Gnomad AMR exome

AF:

0.0599

Gnomad ASJ exome

AF:

0.0417

Gnomad EAS exome

AF:

0.0281

Gnomad FIN exome

AF:

0.0791

Gnomad NFE exome

AF:

0.0874

Gnomad OTH exome

AF:

0.0715

GnomAD4 exome

AF:

0.00750

AC:

4387

AN:

585148

Hom.:

164

Cov.:

AF XY:

0.00838

AC XY:

2392

AN XY:

285380

show subpopulations

African (AFR)

AF:

0.0325

AC:

180

AN:

5532

American (AMR)

AF:

0.0459

AC:

505

AN:

10994

Ashkenazi Jewish (ASJ)

AF:

0.00477

AC:

AN:

11100

East Asian (EAS)

AF:

0.00624

AC:

AN:

13786

South Asian (SAS)

AF:

0.0136

AC:

292

AN:

21410

European-Finnish (FIN)

AF:

0.0215

AC:

395

AN:

18350

Middle Eastern (MID)

AF:

0.00428

AC:

AN:

1870

European-Non Finnish (NFE)

AF:

0.00559

AC:

2676

AN:

478582

Other (OTH)

AF:

0.00816

AC:

192

AN:

23524

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

160

320

480

640

800

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<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:

0.000749

AC:

AN:

53398

Hom.:

Cov.:

AF XY:

0.000680

AC XY:

AN XY:

26458

show subpopulations

African (AFR)

AF:

0.00223

AC:

AN:

7620

American (AMR)

AF:

0.000742

AC:

AN:

5388

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1864

East Asian (EAS)

AF:

0.00

AC:

AN:

1954

South Asian (SAS)

AF:

0.000742

AC:

AN:

1348

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4888

Middle Eastern (MID)

AF:

0.00

AC:

AN:

154

European-Non Finnish (NFE)

AF:

0.000619

AC:

AN:

29088

Other (OTH)

AF:

0.00

AC:

AN:

870

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 26, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

3.5

(source)

DANN

Benign

0.32

PhyloP100

0.0

PromoterAI

-0.10

Neutral

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over