rs33990840

Positions:

• chr1-206116320-C-G
• chr1-206116320-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000707.5(AVPR1B):​c.571G>C​(p.Gly191Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0459 in 1,613,466 control chromosomes in the GnomAD database, including 2,137 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.061 (355 hom., cov: 32)
  • Exomes 𝑓: 0.044 (1782 hom.)
• Consequence: AVPR1B NM_000707.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.316

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0038514733).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AVPR1B	NM_000707.5	c.571G>C	p.Gly191Arg	missense_variant	1/2	ENST00000367126.5	NP_000698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AVPR1B	ENST00000367126.5	c.571G>C	p.Gly191Arg	missense_variant	1/2	1	NM_000707.5	ENSP00000356094.4
AVPR1B	ENST00000612906.1	n.36+1344G>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0611 AC: 9299 AN: 152130 Hom.: 355 Cov.: 32

Gnomad AFR AF: 0.0992

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0376

Gnomad ASJ AF: 0.0919

Gnomad EAS AF: 0.00617

Gnomad SAS AF: 0.0474

Gnomad FIN AF: 0.0683

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0461

Gnomad OTH AF: 0.0583

GnomAD3 exomes AF: 0.0500 AC: 12409 AN: 248102 Hom.: 411 AF XY: 0.0501 AC XY: 6757 AN XY: 134804

Gnomad AFR exome AF: 0.103

Gnomad AMR exome AF: 0.0271

Gnomad ASJ exome AF: 0.0992

Gnomad EAS exome AF: 0.00562

Gnomad SAS exome AF: 0.0511

Gnomad FIN exome AF: 0.0609

Gnomad NFE exome AF: 0.0497

Gnomad OTH exome AF: 0.0596

GnomAD4 exome AF: 0.0443 AC: 64753 AN: 1461218 Hom.: 1782 Cov.: 34 AF XY: 0.0449 AC XY: 32616 AN XY: 726950

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.0292

Gnomad4 ASJ exome AF: 0.0973

Gnomad4 EAS exome AF: 0.00741

Gnomad4 SAS exome AF: 0.0522

Gnomad4 FIN exome AF: 0.0604

Gnomad4 NFE exome AF: 0.0410

Gnomad4 OTH exome AF: 0.0514

GnomAD4 genome AF: 0.0612 AC: 9312 AN: 152248 Hom.: 355 Cov.: 32 AF XY: 0.0609 AC XY: 4531 AN XY: 74450

Gnomad4 AFR AF: 0.0994

Gnomad4 AMR AF: 0.0376

Gnomad4 ASJ AF: 0.0919

Gnomad4 EAS AF: 0.00618

Gnomad4 SAS AF: 0.0472

Gnomad4 FIN AF: 0.0683

Gnomad4 NFE AF: 0.0461

Gnomad4 OTH AF: 0.0568

Alfa AF: 0.0433 Hom.: 120

Bravo AF: 0.0606

Asia WGS AF: 0.0260 AC: 93 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_noAF	Benign	-0.38
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.036	T
LIST_S2	Benign	0.31	T
MetaRNN	Benign	0.0039	T
PROVEAN	Benign	0.81	N
Sift	Benign	0.30	T
Sift4G	Benign	0.50	T
Vest4		0.12
gMVP		0.76

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

LitVar

Other links and lift over

dbSNP: rs33990840; hg19: chr1-206225011;