5-115963280-C-T

Position:

• chr5-115963280-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_173800.5(LVRN):​c.663C>T​(p.Phe221=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 1,611,318 control chromosomes in the GnomAD database, including 136,064 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 0.37 (11107 hom., cov: 31)
  • Exomes 𝑓: 0.41 (124957 hom.)
• Consequence: LVRN NM_173800.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP7: Synonymous conserved (PhyloP=1.18 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LVRN	NM_173800.5	c.663C>T	p.Phe221=	synonymous_variant	1/20	ENST00000357872.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LVRN	ENST00000357872.9	c.663C>T	p.Phe221=	synonymous_variant	1/20	1	NM_173800.5	P1
LVRN	ENST00000504467.5	c.663C>T	p.Phe221=	synonymous_variant, NMD_transcript_variant	1/20	1

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56590 AN: 151762 Hom.: 11111 Cov.: 31

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.362

GnomAD3 exomes AF: 0.409 AC: 97865 AN: 239172 Hom.: 20447 AF XY: 0.413 AC XY: 54086 AN XY: 130846

Gnomad AFR exome AF: 0.255

Gnomad AMR exome AF: 0.403

Gnomad ASJ exome AF: 0.357

Gnomad EAS exome AF: 0.427

Gnomad SAS exome AF: 0.472

Gnomad FIN exome AF: 0.444

Gnomad NFE exome AF: 0.409

Gnomad OTH exome AF: 0.410

GnomAD4 exome AF: 0.412 AC: 601583 AN: 1459438 Hom.: 124957 Cov.: 53 AF XY: 0.414 AC XY: 300524 AN XY: 725888

Gnomad4 AFR exome AF: 0.247

Gnomad4 AMR exome AF: 0.403

Gnomad4 ASJ exome AF: 0.360

Gnomad4 EAS exome AF: 0.397

Gnomad4 SAS exome AF: 0.473

Gnomad4 FIN exome AF: 0.448

Gnomad4 NFE exome AF: 0.413

Gnomad4 OTH exome AF: 0.409

GnomAD4 genome AF: 0.373 AC: 56592 AN: 151880 Hom.: 11107 Cov.: 31 AF XY: 0.377 AC XY: 27974 AN XY: 74228

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.364

Alfa AF: 0.397 Hom.: 12347

Bravo AF: 0.361

Asia WGS AF: 0.446 AC: 1549 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	11
DANN	Benign	0.79

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: rs1445708; hg19: chr5-115298977; COSMIC: COSV63496634;