Genetic Variant LVRN:p.Asp314Asp (chr5-115984673-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BS1BS2

The NM_173800.5(LVRN):c.942C>T(p.Asp314Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0161 in 1,613,582 control chromosomes in the GnomAD database, including 244 homozygotes. 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: 𝑓 0.012 ( 9 hom., cov: 32)

Exomes 𝑓: 0.017 ( 235 hom. )

Consequence

LVRN
NM_173800.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.311

Publications

6 publications found

Variant links:

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]

LVRN links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP7

Synonymous conserved (PhyloP=0.311 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0119 (1815/152248) while in subpopulation NFE AF = 0.0171 (1160/68004). AF 95% confidence interval is 0.0162. There are 9 homozygotes in GnomAd4. There are 885 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
LVRN	NM_173800.5 link	c.942C>T	p.Asp314Asp	synonymous_variant	Exon 3 of 20	ENST00000357872.9	NP_776161.3
LVRN	XM_047416913.1 link	c.249C>T	p.Asp83Asp	synonymous_variant	Exon 3 of 20		XP_047272869.1
LVRN	XM_047416914.1 link	c.153C>T	p.Asp51Asp	synonymous_variant	Exon 3 of 20		XP_047272870.1
LVRN	XM_047416915.1 link	c.153C>T	p.Asp51Asp	synonymous_variant	Exon 3 of 20		XP_047272871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LVRN	ENST00000357872.9 link	c.942C>T	p.Asp314Asp	synonymous_variant	Exon 3 of 20	1	NM_173800.5	ENSP00000350541.4
LVRN	ENST00000504467.5 link	n.942C>T		non_coding_transcript_exon_variant	Exon 3 of 20	1		ENSP00000423604.1

Frequencies

GnomAD3 genomes

AF:

0.0119

AC:

1816

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0108

Gnomad ASJ

AF:

0.0274

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0145

Gnomad FIN

AF:

0.0138

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0171

Gnomad OTH

AF:

0.0115

GnomAD2 exomes

AF:

0.0140

AC:

3524

AN:

250924

AF XY:

0.0147

show subpopulations

Gnomad AFR exome

AF:

0.00302

Gnomad AMR exome

AF:

0.00659

Gnomad ASJ exome

AF:

0.0300

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0158

Gnomad NFE exome

AF:

0.0182

Gnomad OTH exome

AF:

0.0162

GnomAD4 exome

AF:

0.0165

AC:

24166

AN:

1461334

Hom.:

235

Cov.:

AF XY:

0.0166

AC XY:

12078

AN XY:

726962

show subpopulations

African (AFR)

AF:

0.00311

AC:

104

AN:

33444

American (AMR)

AF:

0.00666

AC:

297

AN:

44622

Ashkenazi Jewish (ASJ)

AF:

0.0308

AC:

805

AN:

26118

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39688

South Asian (SAS)

AF:

0.0136

AC:

1173

AN:

86240

European-Finnish (FIN)

AF:

0.0166

AC:

887

AN:

53398

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0178

AC:

19816

AN:

1111704

Other (OTH)

AF:

0.0166

AC:

1004

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

1353

2706

4060

5413

6766

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

750

1500

2250

3000

3750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0119

AC:

1815

AN:

152248

Hom.:

Cov.:

AF XY:

0.0119

AC XY:

885

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.00361

AC:

150

AN:

41556

American (AMR)

AF:

0.0108

AC:

165

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0274

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5174

South Asian (SAS)

AF:

0.0143

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0138

AC:

146

AN:

10608

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0171

AC:

1160

AN:

68004

Other (OTH)

AF:

0.0114

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

188

283

377

471

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0170

Hom.:

159

Bravo

AF:

0.0109

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.0166

EpiControl

AF:

0.0208

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

2.3

(source)

DANN

Benign

0.28

PhyloP100

0.31

Mutation Taster

=282/18

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over