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GeneBe

1-206116076-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_000707.5(AVPR1B):c.815T>A(p.Ile272Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 7/11 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

AVPR1B
NM_000707.5 missense

Scores

7
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.32
Variant links:
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 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, 0.745

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AVPR1BNM_000707.5 linkuse as main transcriptc.815T>A p.Ile272Asn missense_variant 1/2 ENST00000367126.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AVPR1BENST00000367126.5 linkuse as main transcriptc.815T>A p.Ile272Asn missense_variant 1/21 NM_000707.5 P1
AVPR1BENST00000612906.1 linkuse as main transcriptn.36+1588T>A intron_variant, non_coding_transcript_variant 4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
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 submitterclinical testingAmbry GeneticsMar 08, 2024The c.815T>A (p.I272N) alteration is located in exon 1 (coding exon 1) of the AVPR1B gene. This alteration results from a T to A substitution at nucleotide position 815, causing the isoleucine (I) at amino acid position 272 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.62
BayesDel_noAF
Pathogenic
0.32
Cadd
Pathogenic
28
Dann
Uncertain
0.99
DEOGEN2
Uncertain
0.47
T
LIST_S2
Pathogenic
0.99
D
MetaRNN
Pathogenic
0.75
D
PROVEAN
Pathogenic
-6.3
D
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Vest4
0.66
gMVP
0.99

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-206225255; API