rs17138681

Variant names:

• chr5-116022440-G-A
• rs17138681
• NM_173800.5:c.2806G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-116022440-G-A
• chr5-116022440-G-C

Variant summary

Our verdict is Benign. The variant received -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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• 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
• Publications: 11 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: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173800.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LVRN	NM_173800.5	MANE Select	c.2806G>A	p.Val936Ile	missense	Exon 19 of 20	NP_776161.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LVRN	ENST00000357872.9	TSL:1 MANE Select	c.2806G>A	p.Val936Ile	missense	Exon 19 of 20	ENSP00000350541.4
	LVRN	ENST00000504467.5	TSL:1	n.*587G>A		non_coding_transcript_exon	Exon 19 of 20	ENSP00000423604.1
	LVRN	ENST00000504467.5	TSL:1	n.*587G>A		3_prime_UTR	Exon 19 of 20	ENSP00000423604.1

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

GnomAD2 exomes AF: 0.00840 AC: 1885 AN: 224496 AF XY: 0.00685

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 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

African (AFR) AF: 0.0876 AC: 2669 AN: 30470

American (AMR) AF: 0.00479 AC: 182 AN: 37984

Ashkenazi Jewish (ASJ) AF: 0.0000396 AC: 1 AN: 25224

East Asian (EAS) AF: 0.0190 AC: 725 AN: 38064

South Asian (SAS) AF: 0.000603 AC: 49 AN: 81202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53174

Middle Eastern (MID) AF: 0.00409 AC: 23 AN: 5626

European-Non Finnish (NFE) AF: 0.000163 AC: 175 AN: 1076190

Other (OTH) AF: 0.00617 AC: 360 AN: 58344

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

African (AFR) AF: 0.0897 AC: 3725 AN: 41526

American (AMR) AF: 0.00943 AC: 144 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.0241 AC: 125 AN: 5188

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000368 AC: 25 AN: 68024

Other (OTH) AF: 0.0109 AC: 23 AN: 2106

Alfa AF: 0.0107 Hom.: 155

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

Apr 10, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

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
DEOGEN2	Benign	0.00088	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00099	N
LIST_S2	Benign	0.39	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.83	N
PhyloP100		0.10
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.47	N
REVEL	Benign	0.012
Sift	Benign	0.58	T
Sift4G	Benign	1.0	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
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17138681; hg19: chr5-115358137; COSMIC: COSV63497326; COSMIC: COSV63497326;