rs35608965

Positions:

• chr1-206116919-A-G

Variant summary

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

The NM_000707.5(AVPR1B):​c.-29T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0457 in 1,574,190 control chromosomes in the GnomAD database, including 2,073 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.061 (353 hom., cov: 32)
  • Exomes 𝑓: 0.044 (1720 hom.)
• Consequence: AVPR1B NM_000707.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600

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 (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AVPR1B	NM_000707.5	c.-29T>C		5_prime_UTR_variant	1/2	ENST00000367126.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AVPR1B	ENST00000367126.5	c.-29T>C		5_prime_UTR_variant	1/2	1	NM_000707.5	P1
AVPR1B	ENST00000612906.1	n.36+745T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0611 AC: 9289 AN: 152020 Hom.: 353 Cov.: 32

Gnomad AFR AF: 0.0991

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0377

Gnomad ASJ AF: 0.0919

Gnomad EAS AF: 0.00617

Gnomad SAS AF: 0.0475

Gnomad FIN AF: 0.0680

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0461

Gnomad OTH AF: 0.0590

GnomAD3 exomes AF: 0.0490 AC: 10979 AN: 224204 Hom.: 362 AF XY: 0.0493 AC XY: 5951 AN XY: 120774

Gnomad AFR exome AF: 0.102

Gnomad AMR exome AF: 0.0263

Gnomad ASJ exome AF: 0.0950

Gnomad EAS exome AF: 0.00565

Gnomad SAS exome AF: 0.0494

Gnomad FIN exome AF: 0.0604

Gnomad NFE exome AF: 0.0497

Gnomad OTH exome AF: 0.0575

GnomAD4 exome AF: 0.0440 AC: 62594 AN: 1422052 Hom.: 1720 Cov.: 30 AF XY: 0.0446 AC XY: 31394 AN XY: 704664

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.0288

Gnomad4 ASJ exome AF: 0.0951

Gnomad4 EAS exome AF: 0.00747

Gnomad4 SAS exome AF: 0.0515

Gnomad4 FIN exome AF: 0.0601

Gnomad4 NFE exome AF: 0.0408

Gnomad4 OTH exome AF: 0.0508

GnomAD4 genome AF: 0.0611 AC: 9302 AN: 152138 Hom.: 353 Cov.: 32 AF XY: 0.0608 AC XY: 4522 AN XY: 74386

Gnomad4 AFR AF: 0.0993

Gnomad4 AMR AF: 0.0376

Gnomad4 ASJ AF: 0.0919

Gnomad4 EAS AF: 0.00619

Gnomad4 SAS AF: 0.0474

Gnomad4 FIN AF: 0.0680

Gnomad4 NFE AF: 0.0461

Gnomad4 OTH AF: 0.0575

Alfa AF: 0.0588 Hom.: 94

Bravo AF: 0.0606

Asia WGS AF: 0.0270 AC: 94 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.9
DANN	Benign	0.66

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: rs35608965; hg19: chr1-206224412;