NM_005575.3:c.19+16260A>G

Variant summary

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

The NM_005575.3(LNPEP):​c.19+16260A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 152,034 control chromosomes in the GnomAD database, including 18,720 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 0.49 ( 18720 hom., cov: 32)

Consequence

LNPEP
NM_005575.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0280

Publications

13 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=-0.86).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LNPEPNM_005575.3 linkc.19+16260A>G intron_variant Intron 1 of 17 ENST00000231368.10 NP_005566.2 Q9UIQ6-1
LNPEPXM_047417177.1 linkc.19+16260A>G intron_variant Intron 1 of 15 XP_047273133.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LNPEPENST00000231368.10 linkc.19+16260A>G intron_variant Intron 1 of 17 1 NM_005575.3 ENSP00000231368.5 Q9UIQ6-1

Frequencies

GnomAD3 genomes
AF:
0.494
AC:
75007
AN:
151916
Hom.:
18677
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.557
Gnomad AMI
AF:
0.513
Gnomad AMR
AF:
0.427
Gnomad ASJ
AF:
0.369
Gnomad EAS
AF:
0.444
Gnomad SAS
AF:
0.438
Gnomad FIN
AF:
0.468
Gnomad MID
AF:
0.437
Gnomad NFE
AF:
0.489
Gnomad OTH
AF:
0.476
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.494
AC:
75114
AN:
152034
Hom.:
18720
Cov.:
32
AF XY:
0.491
AC XY:
36494
AN XY:
74288
show subpopulations
African (AFR)
AF:
0.558
AC:
23131
AN:
41462
American (AMR)
AF:
0.427
AC:
6527
AN:
15272
Ashkenazi Jewish (ASJ)
AF:
0.369
AC:
1282
AN:
3470
East Asian (EAS)
AF:
0.444
AC:
2296
AN:
5174
South Asian (SAS)
AF:
0.437
AC:
2105
AN:
4818
European-Finnish (FIN)
AF:
0.468
AC:
4947
AN:
10560
Middle Eastern (MID)
AF:
0.422
AC:
124
AN:
294
European-Non Finnish (NFE)
AF:
0.489
AC:
33220
AN:
67960
Other (OTH)
AF:
0.480
AC:
1015
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1939
3877
5816
7754
9693
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
670
1340
2010
2680
3350
<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:
0.487
Hom.:
7020
Bravo
AF:
0.490
Asia WGS
AF:
0.529
AC:
1839
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
3.1
DANN
Benign
0.61
PhyloP100
0.028
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: rs7713127; hg19: chr5-96288138; COSMIC: COSV51480947; API