rs17138681

Positions:

• chr5-116022440-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_173800.5(LVRN):​c.2806G>A​(p.Val936Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00528 in 1,558,512 control chromosomes in the GnomAD database, including 310 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.027 (178 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (132 hom.)
• Consequence: LVRN NM_173800.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.105

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016358495).
• BP6: Variant 5-116022440-G-A is Benign according to our data. Variant chr5-116022440-G-A is described in ClinVar as [Benign]. Clinvar id is 778868.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LVRN	NM_173800.5	c.2806G>A	p.Val936Ile	missense_variant	19/20	ENST00000357872.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LVRN	ENST00000357872.9	c.2806G>A	p.Val936Ile	missense_variant	19/20	1	NM_173800.5	P1

Frequencies

GnomAD3 genomes AF: 0.0265 AC: 4033 AN: 152116 Hom.: 175 Cov.: 32

Gnomad AFR AF: 0.0897

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00950

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0238

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0106

GnomAD3 exomes AF: 0.00840 AC: 1885 AN: 224496 Hom.: 65 AF XY: 0.00685 AC XY: 836 AN XY: 122010

Gnomad AFR exome AF: 0.0892

Gnomad AMR exome AF: 0.00446

Gnomad ASJ exome AF: 0.000109

Gnomad EAS exome AF: 0.0241

Gnomad SAS exome AF: 0.000503

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000325

Gnomad OTH exome AF: 0.00387

GnomAD4 exome AF: 0.00298 AC: 4184 AN: 1406278 Hom.: 132 Cov.: 27 AF XY: 0.00267 AC XY: 1872 AN XY: 701426

Gnomad4 AFR exome AF: 0.0876

Gnomad4 AMR exome AF: 0.00479

Gnomad4 ASJ exome AF: 0.0000396

Gnomad4 EAS exome AF: 0.0190

Gnomad4 SAS exome AF: 0.000603

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000163

Gnomad4 OTH exome AF: 0.00617

GnomAD4 genome AF: 0.0266 AC: 4047 AN: 152234 Hom.: 178 Cov.: 32 AF XY: 0.0259 AC XY: 1925 AN XY: 74428

Gnomad4 AFR AF: 0.0897

Gnomad4 AMR AF: 0.00943

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0241

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000368

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00577 Hom.: 48

Bravo AF: 0.0296

ESP6500AA AF: 0.0786 AC: 346

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00989 AC: 1201

Asia WGS AF: 0.0230 AC: 79 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.062
DANN	Benign	0.22
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00099	N
LIST_S2	Benign	0.39	T;T
MetaRNN	Benign	0.0016	T;T
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.39	T
Sift4G	Benign	1.0	T;T
Polyphen		0.0030	.;B
Vest4		0.029
MVP		0.088
MPC		0.062
ClinPred		0.00085	T
GERP RS		-6.4
Varity_R		0.035
gMVP		0.069

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17138681; hg19: chr5-115358137; COSMIC: COSV63497326; COSMIC: COSV63497326;