rs17482536

Variant names:

• chr5-115984673-C-G
• rs17482536
• NM_173800.5:c.942C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-115984673-C-G
• chr5-115984673-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_173800.5(LVRN):​c.942C>G​(p.Asp314Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,350 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: LVRN NM_173800.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.311
• Publications: 0 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LVRN	NM_173800.5	c.942C>G	p.Asp314Glu	missense_variant	Exon 3 of 20	ENST00000357872.9	NP_776161.3
LVRN	XM_047416913.1	c.249C>G	p.Asp83Glu	missense_variant	Exon 3 of 20		XP_047272869.1
LVRN	XM_047416914.1	c.153C>G	p.Asp51Glu	missense_variant	Exon 3 of 20		XP_047272870.1
LVRN	XM_047416915.1	c.153C>G	p.Asp51Glu	missense_variant	Exon 3 of 20		XP_047272871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LVRN	ENST00000357872.9	c.942C>G	p.Asp314Glu	missense_variant	Exon 3 of 20	1	NM_173800.5	ENSP00000350541.4
LVRN	ENST00000504467.5	n.942C>G		non_coding_transcript_exon_variant	Exon 3 of 20	1		ENSP00000423604.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461350 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726968

African (AFR) AF: 0.00 AC: 0 AN: 33444

American (AMR) AF: 0.00 AC: 0 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111716

Other (OTH) AF: 0.00 AC: 0 AN: 60356

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Benign	0.82
DEOGEN2	Benign	0.017	.;T
Eigen	Benign	0.14
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.55	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.31	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	.;L
PhyloP100		0.31
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.75	.;N
REVEL	Benign	0.19
Sift	Benign	1.0	.;T
Sift4G	Benign	0.67	T;T
Polyphen		1.0	.;D
Vest4		0.21
MutPred		0.69		.;Gain of sheet (P = 0.1208);
MVP		0.49
MPC		0.41
ClinPred		0.80	D
GERP RS		4.0
Varity_R		0.14
gMVP		0.64
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.54		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.54		Position offset: -5
DS_DL_spliceai		0.52		Position offset: 36

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17482536; hg19: chr5-115320370;