chr1-206115971-T-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_000707.5(AVPR1B):c.920A>G(p.Asp307Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000963 in 1,454,214 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: not found (cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
AVPR1B
NM_000707.5 missense
NM_000707.5 missense
Scores
2
6
1
Clinical Significance
Conservation
PhyloP100: 6.27
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.947
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AVPR1B | NM_000707.5 | c.920A>G | p.Asp307Gly | missense_variant | 1/2 | ENST00000367126.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AVPR1B | ENST00000367126.5 | c.920A>G | p.Asp307Gly | missense_variant | 1/2 | 1 | NM_000707.5 | P1 | |
AVPR1B | ENST00000612906.1 | n.36+1693A>G | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000164 AC: 4AN: 244418Hom.: 0 AF XY: 0.0000303 AC XY: 4AN XY: 132190
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GnomAD4 exome AF: 0.00000963 AC: 14AN: 1454214Hom.: 0 Cov.: 31 AF XY: 0.0000180 AC XY: 13AN XY: 722182
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
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 28, 2022 | The c.920A>G (p.D307G) alteration is located in exon 1 (coding exon 1) of the AVPR1B gene. This alteration results from a A to G substitution at nucleotide position 920, causing the aspartic acid (D) at amino acid position 307 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
T
LIST_S2
Uncertain
D
MetaRNN
Pathogenic
D
PROVEAN
Pathogenic
D
Sift
Uncertain
D
Sift4G
Uncertain
D
Vest4
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at