rs9127

Variant summary

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

The NM_005575.3(LNPEP):​c.*7928G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 151,918 control chromosomes in the GnomAD database, including 22,394 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 0.54 ( 22391 hom., cov: 32)
Exomes 𝑓: 0.36 ( 3 hom. )

Consequence

LNPEP
NM_005575.3 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.754

Publications

33 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]

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=-0.82).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LNPEPNM_005575.3 linkc.*7928G>A 3_prime_UTR_variant Exon 18 of 18 ENST00000231368.10 NP_005566.2 Q9UIQ6-1
LNPEPNM_175920.4 linkc.*7928G>A 3_prime_UTR_variant Exon 18 of 18 NP_787116.2 Q9UIQ6-2
LNPEPXM_047417177.1 linkc.*7928G>A 3_prime_UTR_variant Exon 16 of 16 XP_047273133.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LNPEPENST00000231368.10 linkc.*7928G>A 3_prime_UTR_variant Exon 18 of 18 1 NM_005575.3 ENSP00000231368.5 Q9UIQ6-1

Frequencies

GnomAD3 genomes
AF:
0.541
AC:
82083
AN:
151772
Hom.:
22389
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.497
Gnomad AMI
AF:
0.479
Gnomad AMR
AF:
0.610
Gnomad ASJ
AF:
0.673
Gnomad EAS
AF:
0.621
Gnomad SAS
AF:
0.684
Gnomad FIN
AF:
0.563
Gnomad MID
AF:
0.611
Gnomad NFE
AF:
0.526
Gnomad OTH
AF:
0.550
GnomAD4 exome
AF:
0.357
AC:
10
AN:
28
Hom.:
3
Cov.:
0
AF XY:
0.389
AC XY:
7
AN XY:
18
show subpopulations
African (AFR)
AC:
0
AN:
0
American (AMR)
AC:
0
AN:
0
Ashkenazi Jewish (ASJ)
AC:
0
AN:
0
East Asian (EAS)
AC:
0
AN:
0
South Asian (SAS)
AC:
0
AN:
0
European-Finnish (FIN)
AF:
0.500
AC:
3
AN:
6
Middle Eastern (MID)
AF:
1.00
AC:
2
AN:
2
European-Non Finnish (NFE)
AF:
0.250
AC:
4
AN:
16
Other (OTH)
AF:
0.250
AC:
1
AN:
4
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.438
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
AF:
0.541
AC:
82109
AN:
151890
Hom.:
22391
Cov.:
32
AF XY:
0.546
AC XY:
40552
AN XY:
74224
show subpopulations
African (AFR)
AF:
0.497
AC:
20556
AN:
41398
American (AMR)
AF:
0.609
AC:
9287
AN:
15242
Ashkenazi Jewish (ASJ)
AF:
0.673
AC:
2331
AN:
3466
East Asian (EAS)
AF:
0.621
AC:
3214
AN:
5176
South Asian (SAS)
AF:
0.686
AC:
3306
AN:
4820
European-Finnish (FIN)
AF:
0.563
AC:
5943
AN:
10560
Middle Eastern (MID)
AF:
0.626
AC:
184
AN:
294
European-Non Finnish (NFE)
AF:
0.526
AC:
35704
AN:
67918
Other (OTH)
AF:
0.545
AC:
1147
AN:
2104
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1967
3933
5900
7866
9833
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
728
1456
2184
2912
3640
<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:
0.541
Hom.:
68260
Bravo
AF:
0.544
Asia WGS
AF:
0.566
AC:
1968
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
1.3
DANN
Benign
0.69
PhyloP100
0.75
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs9127; hg19: chr5-96372165; API