5-115962681-C-T

Variant names:

• chr5-115962681-C-T
• rs10062297
• NM_173800.5:c.64C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_173800.5(LVRN):​c.64C>T​(p.Leu22Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 1,609,970 control chromosomes in the GnomAD database, including 517,814 homozygotes. In-silico tool predicts 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 (50763 hom., cov: 31)
  • Exomes 𝑓: 0.80 (467051 hom.)
• Consequence: LVRN NM_173800.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.213
• Publications: 13 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]

ENSG00000294509 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=0.213 with no splicing effect.
• 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	c.64C>T	p.Leu22Leu	synonymous_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	c.64C>T	p.Leu22Leu	synonymous_variant	Exon 1 of 20	1	NM_173800.5	ENSP00000350541.4
LVRN	ENST00000504467.5	n.64C>T		non_coding_transcript_exon_variant	Exon 1 of 20	1		ENSP00000423604.1
ENSG00000294509	ENST00000724005.1	n.*238C>T		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.815 AC: 123909 AN: 151966 Hom.: 50733 Cov.: 31

Gnomad AFR AF: 0.848

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.802

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.763

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.830

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.812

Gnomad OTH AF: 0.787

GnomAD2 exomes AF: 0.783 AC: 187373 AN: 239418 AF XY: 0.777

Gnomad AFR exome AF: 0.850

Gnomad AMR exome AF: 0.775

Gnomad ASJ exome AF: 0.779

Gnomad EAS exome AF: 0.758

Gnomad FIN exome AF: 0.825

Gnomad NFE exome AF: 0.807

Gnomad OTH exome AF: 0.783

GnomAD4 exome AF: 0.799 AC: 1164857 AN: 1457886 Hom.: 467051 Cov.: 87 AF XY: 0.795 AC XY: 576333 AN XY: 725260

African (AFR) AF: 0.844 AC: 28210 AN: 33432

American (AMR) AF: 0.777 AC: 34718 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.782 AC: 20409 AN: 26098

East Asian (EAS) AF: 0.713 AC: 28274 AN: 39678

South Asian (SAS) AF: 0.666 AC: 57380 AN: 86144

European-Finnish (FIN) AF: 0.827 AC: 42191 AN: 51042

Middle Eastern (MID) AF: 0.678 AC: 3452 AN: 5090

European-Non Finnish (NFE) AF: 0.812 AC: 902150 AN: 1111500

Other (OTH) AF: 0.798 AC: 48073 AN: 60222

GnomAD4 genome AF: 0.815 AC: 123994 AN: 152084 Hom.: 50763 Cov.: 31 AF XY: 0.814 AC XY: 60497 AN XY: 74336

African (AFR) AF: 0.848 AC: 35163 AN: 41488

American (AMR) AF: 0.802 AC: 12274 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.786 AC: 2726 AN: 3470

East Asian (EAS) AF: 0.762 AC: 3903 AN: 5120

South Asian (SAS) AF: 0.673 AC: 3241 AN: 4814

European-Finnish (FIN) AF: 0.830 AC: 8794 AN: 10594

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.812 AC: 55180 AN: 67976

Other (OTH) AF: 0.785 AC: 1661 AN: 2116

Alfa AF: 0.806 Hom.: 16229

Bravo AF: 0.814

Asia WGS AF: 0.737 AC: 2562 AN: 3478

EpiCase AF: 0.795

EpiControl AF: 0.791

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.2
DANN	Benign	0.89
PhyloP100		0.21
PromoterAI		0.0096	Neutral
Mutation Taster		=100/0	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: rs10062297; hg19: chr5-115298378; COSMIC: COSV63496338;