5-115963280-C-T

Variant names:

• chr5-115963280-C-T
• rs1445708
• NM_173800.5:c.663C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_173800.5(LVRN):​c.663C>T​(p.Phe221Phe) 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
• Publications: 14 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 -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.

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.663C>T	p.Phe221Phe	synonymous	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.663C>T	p.Phe221Phe	synonymous	Exon 1 of 20	ENSP00000350541.4
	LVRN	ENST00000504467.5	TSL:1	n.663C>T		non_coding_transcript_exon	Exon 1 of 20	ENSP00000423604.1

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

GnomAD2 exomes AF: 0.409 AC: 97865 AN: 239172 AF XY: 0.413

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 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

African (AFR) AF: 0.247 AC: 8264 AN: 33466

American (AMR) AF: 0.403 AC: 17975 AN: 44564

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 9363 AN: 25994

East Asian (EAS) AF: 0.397 AC: 15762 AN: 39660

South Asian (SAS) AF: 0.473 AC: 40652 AN: 85946

European-Finnish (FIN) AF: 0.448 AC: 23427 AN: 52344

Middle Eastern (MID) AF: 0.332 AC: 1897 AN: 5718

European-Non Finnish (NFE) AF: 0.413 AC: 459570 AN: 1111428

Other (OTH) AF: 0.409 AC: 24673 AN: 60318

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

African (AFR) AF: 0.255 AC: 10589 AN: 41452

American (AMR) AF: 0.411 AC: 6276 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1245 AN: 3468

East Asian (EAS) AF: 0.420 AC: 2149 AN: 5120

South Asian (SAS) AF: 0.475 AC: 2280 AN: 4802

European-Finnish (FIN) AF: 0.445 AC: 4693 AN: 10550

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27836 AN: 67888

Other (OTH) AF: 0.364 AC: 767 AN: 2110

Alfa AF: 0.396 Hom.: 15875

Bravo AF: 0.361

Asia WGS AF: 0.446 AC: 1549 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	11
DANN	Benign	0.79
PhyloP100		1.2
Mutation Taster		=298/2	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: rs1445708; hg19: chr5-115298977; COSMIC: COSV63496634;