chr20-3083005-G-A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_000490.5(AVP):​c.294C>T​(p.Cys98Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000066 in 151,506 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

AVP
NM_000490.5 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.188

Publications

12 publications found
Variant links:
Genes affected
AVP (HGNC:894): (arginine vasopressin) This gene encodes a member of the vasopressin/oxytocin family and preproprotein that is proteolytically processed to generate multiple protein products. These products include the neuropeptide hormone arginine vasopressin, and two other peptides, neurophysin 2 and copeptin. Arginine vasopressin is a posterior pituitary hormone that is synthesized in the supraoptic nucleus and paraventricular nucleus of the hypothalamus. Along with its carrier protein, neurophysin 2, it is packaged into neurosecretory vesicles and transported axonally to the nerve endings in the neurohypophysis where it is either stored or secreted into the bloodstream. The precursor is thought to be activated while it is being transported along the axon to the posterior pituitary. Arginine vasopressin acts as a growth factor by enhancing pH regulation through acid-base transport systems. It has a direct antidiuretic action on the kidney, and also causes vasoconstriction of the peripheral vessels. This hormone can contract smooth muscle during parturition and lactation. It is also involved in cognition, tolerance, adaptation and complex sexual and maternal behaviour, as well as in the regulation of water excretion and cardiovascular functions. Mutations in this gene cause autosomal dominant neurohypophyseal diabetes insipidus (ADNDI). This gene is present in a gene cluster with the related gene oxytocin on chromosome 20. [provided by RefSeq, Nov 2015]
AVP Gene-Disease associations (from GenCC):
  • neurohypophyseal diabetes insipidus
    Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP7
Synonymous conserved (PhyloP=0.188 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AVPNM_000490.5 linkc.294C>T p.Cys98Cys synonymous_variant Exon 2 of 3 ENST00000380293.3 NP_000481.2 P01185X5DQP6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AVPENST00000380293.3 linkc.294C>T p.Cys98Cys synonymous_variant Exon 2 of 3 1 NM_000490.5 ENSP00000369647.3 P01185

Frequencies

GnomAD3 genomes
AF:
0.00000660
AC:
1
AN:
151402
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00
AC:
0
AN:
159256
AF XY:
0.00
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
1376650
Hom.:
0
Cov.:
36
AF XY:
0.00
AC XY:
0
AN XY:
683166
African (AFR)
AF:
0.00
AC:
0
AN:
28514
American (AMR)
AF:
0.00
AC:
0
AN:
36620
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24064
East Asian (EAS)
AF:
0.00
AC:
0
AN:
32390
South Asian (SAS)
AF:
0.00
AC:
0
AN:
79244
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
35896
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4152
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1078978
Other (OTH)
AF:
0.00
AC:
0
AN:
56792
GnomAD4 genome
AF:
0.00000660
AC:
1
AN:
151506
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74054
show subpopulations
African (AFR)
AF:
0.0000241
AC:
1
AN:
41456
American (AMR)
AF:
0.00
AC:
0
AN:
15236
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3460
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5114
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4788
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10394
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
292
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67760
Other (OTH)
AF:
0.00
AC:
0
AN:
2100
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
CADD
Benign
7.5
DANN
Benign
0.93
PhyloP100
0.19

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: rs121964884; hg19: chr20-3063651; API