1-206116061-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000707.5(AVPR1B):c.830T>C(p.Ile277Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AVPR1B NM_000707.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.32

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AVPR1B	NM_000707.5	c.830T>C	p.Ile277Thr	missense_variant	1/2	ENST00000367126.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AVPR1B	ENST00000367126.5	c.830T>C	p.Ile277Thr	missense_variant	1/2	1	NM_000707.5	P1
AVPR1B	ENST00000612906.1	n.36+1603T>C		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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 07, 2023

The c.830T>C (p.I277T) alteration is located in exon 1 (coding exon 1) of the AVPR1B gene. This alteration results from a T to C substitution at nucleotide position 830, causing the isoleucine (I) at amino acid position 277 to be replaced by a threonine (T). 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	0.64
BayesDel_noAF	Pathogenic	0.25
Cadd	Pathogenic	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.42	T
LIST_S2	Uncertain	0.88	D
MetaRNN	Uncertain	0.54	D
PROVEAN	Pathogenic	-4.5	D
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.010	D
Vest4		0.58
gMVP		0.91

Splicing

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: chr1-206225270;