chr5-115962778-T-C

Position:

• chr5-115962778-T-C

Variant summary

Our verdict is Benign. Variant got -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. 13/19 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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
LVRN	NM_173800.5	c.161T>C	p.Leu54Ser	missense_variant	1/20	ENST00000357872.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LVRN	ENST00000357872.9	c.161T>C	p.Leu54Ser	missense_variant	1/20	1	NM_173800.5	P1
LVRN	ENST00000504467.5	c.161T>C	p.Leu54Ser	missense_variant, NMD_transcript_variant	1/20	1

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

GnomAD3 exomes AF: 0.782 AC: 188959 AN: 241682 Hom.: 74299 AF XY: 0.776 AC XY: 102504 AN XY: 132078

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 SAS exome AF: 0.663

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

Gnomad4 AFR exome AF: 0.844

Gnomad4 AMR exome AF: 0.777

Gnomad4 ASJ exome AF: 0.782

Gnomad4 EAS exome AF: 0.704

Gnomad4 SAS exome AF: 0.667

Gnomad4 FIN exome AF: 0.828

Gnomad4 NFE exome AF: 0.812

Gnomad4 OTH exome AF: 0.798

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

Gnomad4 AFR AF: 0.848

Gnomad4 AMR AF: 0.801

Gnomad4 ASJ AF: 0.786

Gnomad4 EAS AF: 0.759

Gnomad4 SAS AF: 0.673

Gnomad4 FIN AF: 0.830

Gnomad4 NFE AF: 0.812

Gnomad4 OTH AF: 0.785

Alfa AF: 0.804 Hom.: 69268

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	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;T
MetaRNN	Benign	0.0000011	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.1	.;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Uncertain	0.49	T
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	T
GERP RS		-0.44
Varity_R		0.025
gMVP		0.54

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

LitVar

Other links and lift over

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