dbSNP rs1057808: LNPEP:c.*408T>C (chr5-97028941-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005575.3(LNPEP):c.*408T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.038 in 174,162 control chromosomes in the GnomAD database, including 204 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 0.037 ( 184 hom., cov: 32)

Exomes 𝑓: 0.043 ( 20 hom. )

Consequence

LNPEP
NM_005575.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.193

Publications

7 publications found

Variant links:

Genes affected

LNPEP (HGNC:6656): (leucyl and cystinyl aminopeptidase) This gene encodes a zinc-dependent aminopeptidase that cleaves vasopressin, oxytocin, lys-bradykinin, met-enkephalin, dynorphin A and other peptide hormones. The protein can be secreted in maternal serum, reside in intracellular vesicles with the insulin-responsive glucose transporter GLUT4, or form a type II integral membrane glycoprotein. The protein catalyzes the final step in the conversion of angiotensinogen to angiotensin IV (AT4) and is also a receptor for AT4. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

LNPEP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
LNPEP	NM_005575.3 link	c.*408T>C	3_prime_UTR_variant	Exon 18 of 18	ENST00000231368.10	NP_005566.2	Q9UIQ6-1
LNPEP	NM_175920.4 link	c.*408T>C	3_prime_UTR_variant	Exon 18 of 18		NP_787116.2	Q9UIQ6-2
LNPEP	XM_047417177.1 link	c.*408T>C	3_prime_UTR_variant	Exon 16 of 16		XP_047273133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LNPEP	ENST00000231368.10 link	c.*408T>C		3_prime_UTR_variant	Exon 18 of 18	1	NM_005575.3	ENSP00000231368.5		Q9UIQ6-1
LNPEP	ENST00000395770.3 link	c.*408T>C		3_prime_UTR_variant	Exon 18 of 18	1		ENSP00000379117.3		Q9UIQ6-2

Frequencies

GnomAD3 genomes

AF:

0.0374

AC:

5694

AN:

152158

Hom.:

185

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00965

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.0457

Gnomad ASJ

AF:

0.0704

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0286

Gnomad FIN

AF:

0.0185

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.0551

Gnomad OTH

AF:

0.0566

GnomAD4 exome

AF:

0.0427

AC:

935

AN:

21886

Hom.:

Cov.:

AF XY:

0.0411

AC XY:

453

AN XY:

11034

show subpopulations

African (AFR)

AF:

0.00505

AC:

AN:

198

American (AMR)

AF:

0.0469

AC:

AN:

1578

Ashkenazi Jewish (ASJ)

AF:

0.0704

AC:

AN:

398

East Asian (EAS)

AF:

0.0132

AC:

AN:

756

South Asian (SAS)

AF:

0.0314

AC:

AN:

2070

European-Finnish (FIN)

AF:

0.0163

AC:

AN:

798

Middle Eastern (MID)

AF:

0.0732

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0455

AC:

669

AN:

14704

Other (OTH)

AF:

0.0530

AC:

AN:

1302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

139

186

232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0374

AC:

5690

AN:

152276

Hom.:

184

Cov.:

AF XY:

0.0356

AC XY:

2648

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.00963

AC:

400

AN:

41558

American (AMR)

AF:

0.0456

AC:

698

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0704

AC:

244

AN:

3468

East Asian (EAS)

AF:

0.000386

AC:

AN:

5188

South Asian (SAS)

AF:

0.0286

AC:

138

AN:

4824

European-Finnish (FIN)

AF:

0.0185

AC:

196

AN:

10608

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0552

AC:

3752

AN:

68022

Other (OTH)

AF:

0.0565

AC:

119

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

288

577

865

1154

1442

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<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:

0.0540

Hom.:

302

Bravo

AF:

0.0389

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.1

(source)

DANN

Benign

0.51

PhyloP100

0.19

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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