5-115962778-T-C

Variant names:

• chr5-115962778-T-C
• rs12520255
• NM_173800.5:c.161T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.905
• Publications: 25 publications found

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]

ACMG classification

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.

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.161T>C	p.Leu54Ser	missense	Exon 1 of 20	NP_776161.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LVRN	ENST00000357872.9	TSL:1 MANE Select	c.161T>C	p.Leu54Ser	missense	Exon 1 of 20	ENSP00000350541.4	Q6Q4G3-1
	LVRN	ENST00000504467.5	TSL:1	n.161T>C		non_coding_transcript_exon	Exon 1 of 20	ENSP00000423604.1	Q6Q4G3-2

Frequencies

GnomAD3 genomes AF: 0.815 AC: 123728 AN: 151772 Hom.: 50644 Cov.: 30

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

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.: 96 AF XY: 0.794 AC XY: 576165 AN XY: 725314

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

GnomAD4 genome AF: 0.815 AC: 123813 AN: 151890 Hom.: 50674 Cov.: 30 AF XY: 0.814 AC XY: 60395 AN XY: 74230

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.7
DANN	Benign	0.42
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0061	N
LIST_S2	Benign	0.16	T
MetaRNN	Benign	0.0000011	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.1	N
PhyloP100		-0.91
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.95	N
REVEL	Benign	0.011
Sift	Benign	0.72	T
Sift4G	Benign	0.74	T
Polyphen		0.0	B
Vest4		0.020
MPC		0.10
ClinPred		0.00028	T
GERP RS		-0.44
PromoterAI		0.056	Neutral
Varity_R		0.025
gMVP		0.54
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12520255; hg19: chr5-115298475; COSMIC: COSV63496379;