chr1-206116302-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_000707.5(AVPR1B):c.589C>T(p.Arg197Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000514 in 1,613,430 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000054 ( 0 hom. )
Consequence
AVPR1B
NM_000707.5 missense
NM_000707.5 missense
Scores
6
1
2
Clinical Significance
Conservation
PhyloP100: 2.19
Genes affected
AVPR1B (HGNC:896): (arginine vasopressin receptor 1B) The protein encoded by this gene acts as receptor for arginine vasopressin. This receptor belongs to the subfamily of G-protein coupled receptors which includes AVPR1A, V2R and OXT receptors. Its activity is mediated by G proteins which stimulate a phosphatidylinositol-calcium second messenger system. The receptor is primarily located in the anterior pituitary, where it stimulates ACTH release. It is expressed at high levels in ACTH-secreting pituitary adenomas as well as in bronchial carcinoids responsible for the ectopic ACTH syndrome. A spliced antisense transcript of this gene has been reported but its function is not known. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.804
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AVPR1B | NM_000707.5 | c.589C>T | p.Arg197Trp | missense_variant | 1/2 | ENST00000367126.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AVPR1B | ENST00000367126.5 | c.589C>T | p.Arg197Trp | missense_variant | 1/2 | 1 | NM_000707.5 | P1 | |
AVPR1B | ENST00000612906.1 | n.36+1362C>T | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152226Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
4
AN:
152226
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000322 AC: 8AN: 248080Hom.: 0 AF XY: 0.0000297 AC XY: 4AN XY: 134782
GnomAD3 exomes
AF:
AC:
8
AN:
248080
Hom.:
AF XY:
AC XY:
4
AN XY:
134782
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000541 AC: 79AN: 1461204Hom.: 0 Cov.: 34 AF XY: 0.0000495 AC XY: 36AN XY: 726934
GnomAD4 exome
AF:
AC:
79
AN:
1461204
Hom.:
Cov.:
34
AF XY:
AC XY:
36
AN XY:
726934
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152226Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74376
GnomAD4 genome
?
AF:
AC:
4
AN:
152226
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74376
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 05, 2022 | The c.589C>T (p.R197W) alteration is located in exon 1 (coding exon 1) of the AVPR1B gene. This alteration results from a C to T substitution at nucleotide position 589, causing the arginine (R) at amino acid position 197 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Uncertain
T
LIST_S2
Pathogenic
D
MetaRNN
Pathogenic
D
PROVEAN
Pathogenic
D
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Vest4
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at