5-115962681-C-T

Position:

• chr5-115962681-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_173800.5(LVRN):​c.64C>T​(p.Leu22=) 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

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 -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/exons	MANE	UniProt
LVRN	NM_173800.5	c.64C>T	p.Leu22=	synonymous_variant	1/20	ENST00000357872.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LVRN	ENST00000357872.9	c.64C>T	p.Leu22=	synonymous_variant	1/20	1	NM_173800.5	P1
LVRN	ENST00000504467.5	c.64C>T	p.Leu22=	synonymous_variant, NMD_transcript_variant	1/20	1

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

GnomAD3 exomes AF: 0.783 AC: 187373 AN: 239418 Hom.: 73745 AF XY: 0.777 AC XY: 102176 AN XY: 131552

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 SAS exome AF: 0.662

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

Gnomad4 AFR exome AF: 0.844

Gnomad4 AMR exome AF: 0.777

Gnomad4 ASJ exome AF: 0.782

Gnomad4 EAS exome AF: 0.713

Gnomad4 SAS exome AF: 0.666

Gnomad4 FIN exome AF: 0.827

Gnomad4 NFE exome AF: 0.812

Gnomad4 OTH exome AF: 0.798

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

Gnomad4 AFR AF: 0.848

Gnomad4 AMR AF: 0.802

Gnomad4 ASJ AF: 0.786

Gnomad4 EAS AF: 0.762

Gnomad4 SAS AF: 0.673

Gnomad4 FIN AF: 0.830

Gnomad4 NFE AF: 0.812

Gnomad4 OTH AF: 0.785

Alfa AF: 0.805 Hom.: 15957

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

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: rs10062297; hg19: chr5-115298378; COSMIC: COSV63496338;