Variant rs2303138 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000231368.10(LNPEP):c.2287G>A(p.Ala763Thr) variant causes a missense change. The variant allele was found at a frequency of 0.092 in 1,601,346 control chromosomes in the GnomAD database, including 10,556 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 0.099 ( 1235 hom., cov: 32)

Exomes 𝑓: 0.091 ( 9321 hom. )

Consequence

LNPEP
ENST00000231368.10 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.97

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=0.0055810213).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LNPEP	NM_005575.3 linkuse as main transcript	c.2287G>A	p.Ala763Thr	missense_variant	13/18	ENST00000231368.10	NP_005566.2
LNPEP	NM_175920.4 linkuse as main transcript	c.2245G>A	p.Ala749Thr	missense_variant	13/18		NP_787116.2
LNPEP	XM_047417177.1 linkuse as main transcript	c.2287G>A	p.Ala763Thr	missense_variant	13/16		XP_047273133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LNPEP	ENST00000231368.10 linkuse as main transcript	c.2287G>A	p.Ala763Thr	missense_variant	13/18	1	NM_005575.3	ENSP00000231368	P1	Q9UIQ6-1
LNPEP	ENST00000395770.3 linkuse as main transcript	c.2245G>A	p.Ala749Thr	missense_variant	13/18	1		ENSP00000379117		Q9UIQ6-2

Frequencies

GnomAD3 genomes

AF:

0.0986

AC:

14991

AN:

151964

Hom.:

1236

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0720

Gnomad AMI

AF:

0.130

Gnomad AMR

AF:

0.164

Gnomad ASJ

AF:

0.110

Gnomad EAS

AF:

0.426

Gnomad SAS

AF:

0.166

Gnomad FIN

AF:

0.0725

Gnomad MID

AF:

0.0541

Gnomad NFE

AF:

0.0736

Gnomad OTH

AF:

0.0995

GnomAD3 exomes

AF:

0.132

AC:

32388

AN:

245798

Hom.:

3709

AF XY:

0.127

AC XY:

16930

AN XY:

132934

show subpopulations

Gnomad AFR exome

AF:

0.0661

Gnomad AMR exome

AF:

0.230

Gnomad ASJ exome

AF:

0.108

Gnomad EAS exome

AF:

0.460

Gnomad SAS exome

AF:

0.158

Gnomad FIN exome

AF:

0.0710

Gnomad NFE exome

AF:

0.0703

Gnomad OTH exome

AF:

0.0982

GnomAD4 exome

AF:

0.0914

AC:

132405

AN:

1449264

Hom.:

9321

Cov.:

AF XY:

0.0920

AC XY:

66337

AN XY:

720686

show subpopulations

Gnomad4 AFR exome

AF:

0.0701

Gnomad4 AMR exome

AF:

0.221

Gnomad4 ASJ exome

AF:

0.105

Gnomad4 EAS exome

AF:

0.402

Gnomad4 SAS exome

AF:

0.161

Gnomad4 FIN exome

AF:

0.0711

Gnomad4 NFE exome

AF:

0.0710

Gnomad4 OTH exome

AF:

0.0997

GnomAD4 genome

AF:

0.0985

AC:

14986

AN:

152082

Hom.:

1235

Cov.:

AF XY:

0.102

AC XY:

7562

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0719

Gnomad4 AMR

AF:

0.164

Gnomad4 ASJ

AF:

0.110

Gnomad4 EAS

AF:

0.426

Gnomad4 SAS

AF:

0.166

Gnomad4 FIN

AF:

0.0725

Gnomad4 NFE

AF:

0.0736

Gnomad4 OTH

AF:

0.0980

Alfa

AF:

0.0876

Hom.:

2259

Bravo

AF:

0.108

TwinsUK

AF:

0.0658

AC:

244

ALSPAC

AF:

0.0737

AC:

284

ESP6500AA

AF:

0.0710

AC:

313

ESP6500EA

AF:

0.0742

AC:

638

ExAC

AF:

0.129

AC:

15714

Asia WGS

AF:

0.225

AC:

782

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.064

T;.

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.72

T;T

MetaRNN

Benign

0.0056

T;T

MetaSVM

Benign

-0.70

MutationAssessor

Uncertain

2.2

M;.

MutationTaster

Benign

0.0000014

P;P

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.96

N;N

REVEL

Benign

0.098

Sift

Benign

0.25

T;T

Sift4G

Benign

0.28

T;T

Polyphen

0.62

P;.

Vest4

0.26

MPC

0.72

ClinPred

0.035

GERP RS

5.5

Varity_R

0.45

gMVP

0.36

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