5-116003261-G-T

Variant names:

• chr5-116003261-G-T
• rs17138632
• NM_173800.5:c.1918G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173800.5(LVRN):​c.1918G>T​(p.Val640Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0317 in 1,577,260 control chromosomes in the GnomAD database, including 1,066 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.032 (135 hom., cov: 32)
  • Exomes 𝑓: 0.032 (931 hom.)
• Consequence: LVRN NM_173800.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016208887).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.083 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LVRN	NM_173800.5	MANE Select	c.1918G>T	p.Val640Phe	missense	Exon 12 of 20	NP_776161.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LVRN	ENST00000357872.9	TSL:1 MANE Select	c.1918G>T	p.Val640Phe	missense	Exon 12 of 20	ENSP00000350541.4	Q6Q4G3-1
	LVRN	ENST00000504467.5	TSL:1	n.1918G>T		non_coding_transcript_exon	Exon 12 of 20	ENSP00000423604.1	Q6Q4G3-2
	LVRN	ENST00000503329.5	TSL:2	n.469G>T		non_coding_transcript_exon	Exon 7 of 16	ENSP00000427418.1	Q6Q4G3-4

Frequencies

GnomAD3 genomes AF: 0.0319 AC: 4847 AN: 152012 Hom.: 135 Cov.: 32

Gnomad AFR AF: 0.00602

Gnomad AMI AF: 0.0374

Gnomad AMR AF: 0.0870

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0309

Gnomad FIN AF: 0.0761

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0313

Gnomad OTH AF: 0.0272

GnomAD2 exomes AF: 0.0387 AC: 8726 AN: 225430 AF XY: 0.0373

Gnomad AFR exome AF: 0.00593

Gnomad AMR exome AF: 0.102

Gnomad ASJ exome AF: 0.0299

Gnomad EAS exome AF: 0.00122

Gnomad FIN exome AF: 0.0769

Gnomad NFE exome AF: 0.0297

Gnomad OTH exome AF: 0.0359

GnomAD4 exome AF: 0.0317 AC: 45143 AN: 1425130 Hom.: 931 Cov.: 30 AF XY: 0.0316 AC XY: 22393 AN XY: 709288

African (AFR) AF: 0.00503 AC: 158 AN: 31418

American (AMR) AF: 0.0970 AC: 3551 AN: 36590

Ashkenazi Jewish (ASJ) AF: 0.0310 AC: 786 AN: 25346

East Asian (EAS) AF: 0.00101 AC: 39 AN: 38774

South Asian (SAS) AF: 0.0278 AC: 2229 AN: 80264

European-Finnish (FIN) AF: 0.0768 AC: 4084 AN: 53202

Middle Eastern (MID) AF: 0.0218 AC: 124 AN: 5690

European-Non Finnish (NFE) AF: 0.0296 AC: 32431 AN: 1094852

Other (OTH) AF: 0.0295 AC: 1741 AN: 58994

GnomAD4 genome AF: 0.0319 AC: 4848 AN: 152130 Hom.: 135 Cov.: 32 AF XY: 0.0350 AC XY: 2599 AN XY: 74356

African (AFR) AF: 0.00600 AC: 249 AN: 41510

American (AMR) AF: 0.0869 AC: 1327 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0245 AC: 85 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5172

South Asian (SAS) AF: 0.0311 AC: 150 AN: 4822

European-Finnish (FIN) AF: 0.0761 AC: 803 AN: 10556

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0313 AC: 2129 AN: 68002

Other (OTH) AF: 0.0269 AC: 57 AN: 2116

Alfa AF: 0.0294 Hom.: 345

Bravo AF: 0.0297

TwinsUK AF: 0.0351 AC: 130

ALSPAC AF: 0.0311 AC: 120

ESP6500AA AF: 0.00568 AC: 25

ESP6500EA AF: 0.0317 AC: 272

ExAC AF: 0.0372 AC: 4513

Asia WGS AF: 0.0110 AC: 39 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.093
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.067
Sift	Benign	0.25	T
Sift4G	Benign	0.44	T
Polyphen		0.67	P
Vest4		0.10
MPC		0.18
ClinPred		0.025	T
GERP RS		-0.94
Varity_R		0.067
gMVP		0.47
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs17138632; hg19: chr5-115338958;