rs7712021

chr5-116001165-T-C

Variant summary

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

The NM_173800.5(LVRN):c.1746T>C(p.Asn582=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,613,368 control chromosomes in the GnomAD database, including 85,042 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 0.32 (7998 hom., cov: 32)
  • Exomes 𝑓: 0.32 (77044 hom.)
• Consequence: LVRN NM_173800.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73

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=-0.53).
• BP7: Synonymous conserved (PhyloP=1.73 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LVRN	NM_173800.5	c.1746T>C	p.Asn582=	synonymous_variant	10/20	ENST00000357872.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LVRN	ENST00000357872.9	c.1746T>C	p.Asn582=	synonymous_variant	10/20	1	NM_173800.5	P1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48741 AN: 151878 Hom.: 7995 Cov.: 32

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.312

GnomAD3 exomes AF: 0.287 AC: 72106 AN: 250986 Hom.: 11188 AF XY: 0.286 AC XY: 38845 AN XY: 135668

Gnomad AFR exome AF: 0.320

Gnomad AMR exome AF: 0.193

Gnomad ASJ exome AF: 0.304

Gnomad EAS exome AF: 0.227

Gnomad SAS exome AF: 0.152

Gnomad FIN exome AF: 0.356

Gnomad NFE exome AF: 0.342

Gnomad OTH exome AF: 0.306

GnomAD4 exome AF: 0.320 AC: 467878 AN: 1461372 Hom.: 77044 Cov.: 39 AF XY: 0.316 AC XY: 229594 AN XY: 726966

Gnomad4 AFR exome AF: 0.324

Gnomad4 AMR exome AF: 0.203

Gnomad4 ASJ exome AF: 0.300

Gnomad4 EAS exome AF: 0.247

Gnomad4 SAS exome AF: 0.153

Gnomad4 FIN exome AF: 0.351

Gnomad4 NFE exome AF: 0.340

Gnomad4 OTH exome AF: 0.312

GnomAD4 genome AF: 0.321 AC: 48768 AN: 151996 Hom.: 7998 Cov.: 32 AF XY: 0.317 AC XY: 23570 AN XY: 74286

Gnomad4 AFR AF: 0.324

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.360

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.309

Alfa AF: 0.329 Hom.: 4115

Bravo AF: 0.316

Asia WGS AF: 0.217 AC: 757 AN: 3478

EpiCase AF: 0.346

EpiControl AF: 0.340

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	4.3
Dann	Benign	0.65

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: rs7712021; hg19: chr5-115336862; COSMIC: COSV63496011;