chr1-206110295-C-T

Variant names:

• chr1-206110295-C-T
• NM_000707.5:c.1169G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000707.5(AVPR1B):​c.1169G>A​(p.Ser390Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: AVPR1B NM_000707.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.320
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058030725).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000707.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AVPR1B	NM_000707.5	MANE Select	c.1169G>A	p.Ser390Asn	missense	Exon 2 of 2	NP_000698.1	P47901

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AVPR1B	ENST00000367126.5	TSL:1 MANE Select	c.1169G>A	p.Ser390Asn	missense	Exon 2 of 2	ENSP00000356094.4	P47901
	AVPR1B	ENST00000612906.1	TSL:4	n.265G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.2
DANN	Benign	0.68
DEOGEN2	Benign	0.093	T
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.058	T
PhyloP100		-0.32
PROVEAN	Benign	-0.23	N
Sift	Benign	0.43	T
Sift4G	Benign	0.21	T
Vest4		0.083
gMVP		0.55

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

Other links and lift over

hg19: chr1-206231036;