Variant rs11746232 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005575.3(LNPEP):c.2887A>G(p.Ile963Val) variant causes a missense change. The variant allele was found at a frequency of 0.0927 in 1,604,980 control chromosomes in the GnomAD database, including 7,823 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.078 ( 569 hom., cov: 32)

Exomes 𝑓: 0.094 ( 7254 hom. )

Consequence

LNPEP
NM_005575.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.58

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019505918).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LNPEP	NM_005575.3 linkuse as main transcript	c.2887A>G	p.Ile963Val	missense_variant	17/18	ENST00000231368.10	NP_005566.2	Q9UIQ6-1
LNPEP	NM_175920.4 linkuse as main transcript	c.2845A>G	p.Ile949Val	missense_variant	17/18		NP_787116.2	Q9UIQ6-2
LNPEP	XM_047417177.1 linkuse as main transcript	c.2584A>G	p.Ile862Val	missense_variant	15/16		XP_047273133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LNPEP	ENST00000231368.10 linkuse as main transcript	c.2887A>G	p.Ile963Val	missense_variant	17/18	1	NM_005575.3	ENSP00000231368.5		Q9UIQ6-1
LNPEP	ENST00000395770.3 linkuse as main transcript	c.2845A>G	p.Ile949Val	missense_variant	17/18	1		ENSP00000379117.3		Q9UIQ6-2

Frequencies

GnomAD3 genomes

AF:

0.0779

AC:

11853

AN:

152160

Hom.:

570

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0329

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.0791

Gnomad ASJ

AF:

0.145

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.151

Gnomad FIN

AF:

0.0959

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0991

Gnomad OTH

AF:

0.101

GnomAD3 exomes

AF:

0.0914

AC:

22947

AN:

251122

Hom.:

1338

AF XY:

0.0980

AC XY:

13295

AN XY:

135718

show subpopulations

Gnomad AFR exome

AF:

0.0302

Gnomad AMR exome

AF:

0.0563

Gnomad ASJ exome

AF:

0.140

Gnomad EAS exome

AF:

0.00141

Gnomad SAS exome

AF:

0.143

Gnomad FIN exome

AF:

0.0982

Gnomad NFE exome

AF:

0.105

Gnomad OTH exome

AF:

0.107

GnomAD4 exome

AF:

0.0942

AC:

136892

AN:

1452702

Hom.:

7254

Cov.:

AF XY:

0.0972

AC XY:

70288

AN XY:

723268

show subpopulations

Gnomad4 AFR exome

AF:

0.0299

Gnomad4 AMR exome

AF:

0.0595

Gnomad4 ASJ exome

AF:

0.140

Gnomad4 EAS exome

AF:

0.000756

Gnomad4 SAS exome

AF:

0.147

Gnomad4 FIN exome

AF:

0.102

Gnomad4 NFE exome

AF:

0.0949

Gnomad4 OTH exome

AF:

0.0972

GnomAD4 genome

AF:

0.0778

AC:

11850

AN:

152278

Hom.:

569

Cov.:

AF XY:

0.0784

AC XY:

5836

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0329

Gnomad4 AMR

AF:

0.0789

Gnomad4 ASJ

AF:

0.145

Gnomad4 EAS

AF:

0.00212

Gnomad4 SAS

AF:

0.151

Gnomad4 FIN

AF:

0.0959

Gnomad4 NFE

AF:

0.0991

Gnomad4 OTH

AF:

0.0992

Alfa

AF:

0.0973

Hom.:

2081

Bravo

AF:

0.0724

TwinsUK

AF:

0.0971

AC:

360

ALSPAC

AF:

0.0916

AC:

353

ESP6500AA

AF:

0.0322

AC:

142

ESP6500EA

AF:

0.0960

AC:

826

ExAC

AF:

0.0938

AC:

11386

Asia WGS

AF:

0.0590

AC:

207

AN:

3476

EpiCase

AF:

0.112

EpiControl

AF:

0.111

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.058

T;.

Eigen

Benign

0.059

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.68

T;T

MetaRNN

Benign

0.0020

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;.

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.73

N;N

REVEL

Benign

0.095

Sift

Benign

0.051

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.0060

B;.

Vest4

0.032

MPC

0.18

ClinPred

0.016

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.37

gMVP

0.26

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over