rs12520255

Variant names:

• chr5-115962778-T-A
• rs12520255
• NM_173800.5:c.161T>A

Your query was ambiguous. Multiple possible variants found:

• chr5-115962778-T-A
• chr5-115962778-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_173800.5(LVRN):​c.161T>A​(p.Leu54*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,834 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. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LVRN NM_173800.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.905
• Publications: 25 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LVRN	NM_173800.5	c.161T>A	p.Leu54*	stop_gained	Exon 1 of 20	ENST00000357872.9	NP_776161.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LVRN	ENST00000357872.9	c.161T>A	p.Leu54*	stop_gained	Exon 1 of 20	1	NM_173800.5	ENSP00000350541.4
LVRN	ENST00000504467.5	n.161T>A		non_coding_transcript_exon_variant	Exon 1 of 20	1		ENSP00000423604.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458834 Hom.: 0 Cov.: 96 AF XY: 0.00000138 AC XY: 1 AN XY: 725362

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26074

East Asian (EAS) AF: 0.00 AC: 0 AN: 39630

South Asian (SAS) AF: 0.00 AC: 0 AN: 86180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110528

Other (OTH) AF: 0.00 AC: 0 AN: 60266

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 115643

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	34
DANN	Benign	0.92
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.025	N
PhyloP100		-0.91
Vest4		0.070
GERP RS		-0.44
PromoterAI		-0.0052	Neutral
Mutation Taster		=24/176	disease causing (fs/PTC)

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: rs12520255; hg19: chr5-115298475;