dbSNP rs17138632: LVRN:p.Val640Ile (chr5-116003261-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173800.5(LVRN):c.1918G>A(p.Val640Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,425,776 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.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LVRN
NM_173800.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0930

Publications

11 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05921772).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LVRN	NM_173800.5	MANE Select	c.1918G>A	p.Val640Ile	missense	Exon 12 of 20	NP_776161.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LVRN	ENST00000357872.9	TSL:1 MANE Select	c.1918G>A	p.Val640Ile	missense	Exon 12 of 20	ENSP00000350541.4	Q6Q4G3-1
LVRN	ENST00000504467.5	TSL:1	n.1918G>A		non_coding_transcript_exon	Exon 12 of 20	ENSP00000423604.1	Q6Q4G3-2
LVRN	ENST00000503329.5	TSL:2	n.469G>A		non_coding_transcript_exon	Exon 7 of 16	ENSP00000427418.1	Q6Q4G3-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000444

AC:

AN:

225430

AF XY:

0.00000816

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000938

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1425776

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

709610

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31424

American (AMR)

AF:

0.00

AC:

AN:

36646

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25352

East Asian (EAS)

AF:

0.00

AC:

AN:

38774

South Asian (SAS)

AF:

0.00

AC:

AN:

80286

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53220

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

0.00000183

AC:

AN:

1095378

Other (OTH)

AF:

0.00

AC:

AN:

59006

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

9.0

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.0031

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.67

M_CAP

Benign

0.0036

MetaRNN

Benign

0.059

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.97

PhyloP100

0.093

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.22

REVEL

Benign

0.065

Sift

Benign

0.32

Sift4G

Benign

0.49

Polyphen

0.0020

Vest4

0.022

MutPred

0.20

Loss of disorder (P = 0.1507)

MVP

0.25

MPC

0.062

ClinPred

0.036

GERP RS

-0.94

Varity_R

0.033

gMVP

0.098

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over