Genetic Variant NM_173800.5:c.2806G>C (chr5-116022440-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173800.5(LVRN):c.2806G>C(p.Val936Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000711 in 1,406,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V936I) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

LVRN
NM_173800.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.105

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.069449425).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173800.5. 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
	LVRN	NM_173800.5	MANE Select	c.2806G>C	p.Val936Leu	missense	Exon 19 of 20	NP_776161.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LVRN	ENST00000357872.9	TSL:1 MANE Select	c.2806G>C	p.Val936Leu	missense	Exon 19 of 20	ENSP00000350541.4
LVRN	ENST00000504467.5	TSL:1	n.*587G>C		non_coding_transcript_exon	Exon 19 of 20	ENSP00000423604.1
LVRN	ENST00000504467.5	TSL:1	n.*587G>C		3_prime_UTR	Exon 19 of 20	ENSP00000423604.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.11e-7

AC:

AN:

1406444

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

701504

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30580

American (AMR)

AF:

0.00

AC:

AN:

37988

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25224

East Asian (EAS)

AF:

0.00

AC:

AN:

38086

South Asian (SAS)

AF:

0.00

AC:

AN:

81202

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53174

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5626

European-Non Finnish (NFE)

AF:

9.29e-7

AC:

AN:

1076200

Other (OTH)

AF:

0.00

AC:

AN:

58364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.11

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.00039

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.59

M_CAP

Benign

0.0065

MetaRNN

Benign

0.069

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

0.10

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.010

REVEL

Benign

0.037

Sift

Benign

0.11

Sift4G

Benign

0.29

Polyphen

0.017

Vest4

0.12

MutPred

0.53

Gain of helix (P = 0.0854)

MVP

0.088

MPC

0.076

ClinPred

0.14

GERP RS

-6.4

Varity_R

0.071

gMVP

0.17

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over