Genetic Variant LVRN:p.Leu54Ser (chr5-115962778-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_173800.5(LVRN):c.161T>C(p.Leu54Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 1,610,624 control chromosomes in the GnomAD database, including 517,701 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.82 ( 50674 hom., cov: 30)

Exomes 𝑓: 0.80 ( 467027 hom. )

Consequence

LVRN
NM_173800.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.905

Publications

25 publications found

Variant links:

Genes affected

LVRN (HGNC:26904): (laeverin) Predicted to enable metalloaminopeptidase activity; peptide binding activity; and zinc ion binding activity. Predicted to be involved in several processes, including peptide catabolic process; proteolysis; and regulation of blood pressure. Predicted to be integral component of membrane. Predicted to be active in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

LVRN links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0556927E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LVRN	NM_173800.5 link	c.161T>C	p.Leu54Ser	missense_variant	Exon 1 of 20	ENST00000357872.9	NP_776161.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LVRN	ENST00000357872.9 link	c.161T>C	p.Leu54Ser	missense_variant	Exon 1 of 20	1	NM_173800.5	ENSP00000350541.4
LVRN	ENST00000504467.5 link	n.161T>C		non_coding_transcript_exon_variant	Exon 1 of 20	1		ENSP00000423604.1

Frequencies

GnomAD3 genomes

AF:

0.815

AC:

123728

AN:

151772

Hom.:

50644

Cov.:

show subpopulations

Gnomad AFR

AF:

0.848

Gnomad AMI

AF:

0.927

Gnomad AMR

AF:

0.801

Gnomad ASJ

AF:

0.786

Gnomad EAS

AF:

0.760

Gnomad SAS

AF:

0.673

Gnomad FIN

AF:

0.830

Gnomad MID

AF:

0.709

Gnomad NFE

AF:

0.812

Gnomad OTH

AF:

0.787

GnomAD2 exomes

AF:

0.782

AC:

188959

AN:

241682

AF XY:

0.776

show subpopulations

Gnomad AFR exome

AF:

0.847

Gnomad AMR exome

AF:

0.774

Gnomad ASJ exome

AF:

0.778

Gnomad EAS exome

AF:

0.754

Gnomad FIN exome

AF:

0.828

Gnomad NFE exome

AF:

0.805

Gnomad OTH exome

AF:

0.783

GnomAD4 exome

AF:

0.799

AC:

1165132

AN:

1458734

Hom.:

467027

Cov.:

AF XY:

0.794

AC XY:

576165

AN XY:

725314

show subpopulations

African (AFR)

AF:

0.844

AC:

28225

AN:

33430

American (AMR)

AF:

0.777

AC:

34668

AN:

44634

Ashkenazi Jewish (ASJ)

AF:

0.782

AC:

20391

AN:

26072

East Asian (EAS)

AF:

0.704

AC:

27894

AN:

39622

South Asian (SAS)

AF:

0.667

AC:

57450

AN:

86176

European-Finnish (FIN)

AF:

0.828

AC:

43329

AN:

52318

Middle Eastern (MID)

AF:

0.679

AC:

3889

AN:

5730

European-Non Finnish (NFE)

AF:

0.812

AC:

901189

AN:

1110488

Other (OTH)

AF:

0.798

AC:

48097

AN:

60264

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

15917

31835

47752

63670

79587

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20838

41676

62514

83352

104190

<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:

0.815

AC:

123813

AN:

151890

Hom.:

50674

Cov.:

AF XY:

0.814

AC XY:

60395

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.848

AC:

35135

AN:

41438

American (AMR)

AF:

0.801

AC:

12248

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.786

AC:

2726

AN:

3466

East Asian (EAS)

AF:

0.759

AC:

3847

AN:

5066

South Asian (SAS)

AF:

0.673

AC:

3229

AN:

4798

European-Finnish (FIN)

AF:

0.830

AC:

8777

AN:

10574

Middle Eastern (MID)

AF:

0.704

AC:

207

AN:

294

European-Non Finnish (NFE)

AF:

0.812

AC:

55143

AN:

67946

Other (OTH)

AF:

0.785

AC:

1657

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1159

2318

3476

4635

5794

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

872

1744

2616

3488

4360

<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:

0.805

Hom.:

115643

Bravo

AF:

0.814

TwinsUK

AF:

0.817

AC:

3029

ALSPAC

AF:

0.810

AC:

3123

ESP6500AA

AF:

0.847

AC:

3696

ESP6500EA

AF:

0.811

AC:

6914

ExAC

AF:

0.779

AC:

94023

Asia WGS

AF:

0.739

AC:

2570

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.7

(source)

DANN

Benign

0.42

DEOGEN2

Benign

0.0022

.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0061

LIST_S2

Benign

0.16

T;T

MetaRNN

Benign

0.0000011

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.1

.;N

PhyloP100

-0.91

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.95

.;N

REVEL

Benign

0.011

Sift

Benign

0.72

.;T

Sift4G

Benign

0.74

T;T

Polyphen

0.0

.;B

Vest4

0.020

MPC

0.10

ClinPred

0.00028

GERP RS

-0.44

PromoterAI

0.056

Neutral

(source)

Varity_R

0.025

gMVP

0.54

Mutation Taster

=300/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over