rs1445708

chr5-115963280-C-Achr5-115963280-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_173800.5(LVRN):c.663C>A(p.Phe221Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LVRN NM_173800.5 missense
• 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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.98

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LVRN	NM_173800.5	c.663C>A	p.Phe221Leu	missense_variant	1/20	ENST00000357872.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LVRN	ENST00000357872.9	c.663C>A	p.Phe221Leu	missense_variant	1/20	1	NM_173800.5	P1
LVRN	ENST00000504467.5	c.663C>A	p.Phe221Leu	missense_variant, NMD_transcript_variant	1/20	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000418 AC: 1 AN: 239172 Hom.: 0 AF XY: 0.00000764 AC XY: 1 AN XY: 130846

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000943

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459566 Hom.: 0 Cov.: 53 AF XY: 0.00000138 AC XY: 1 AN XY: 725958

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
Cadd	Uncertain	23
Dann	Uncertain	1.0
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.021	T
MetaRNN	Pathogenic	0.98	D;D
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.051	P;P
PrimateAI	Uncertain	0.65	T
Sift4G	Uncertain	0.030	D;D
Polyphen		1.0	.;D
Vest4		0.61
MutPred		0.89		.;Gain of sheet (P = 0.0827);
MVP		0.61
MPC		0.46
ClinPred		0.97	D
GERP RS		3.7
Varity_R		0.67
gMVP		0.76

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;