rs28373064

Variant names:

• chr1-206117775-T-C
• rs28373064
• ENST00000425896.1:n.-8T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000425896.1(AVPR1B-DT):​n.-8T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,110 control chromosomes in the GnomAD database, including 2,882 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 0.19 (2881 hom., cov: 31)
  • Exomes 𝑓: 0.12 (1 hom.)
• Consequence: AVPR1B-DT ENST00000425896.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.362
• Publications: 12 publications found

Genes affected

AVPR1B-DT (HGNC:55832): (AVPR1B divergent transcript)

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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AVPR1B-DT	NR_186693.1	n.-8T>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AVPR1B-DT	ENST00000425896.1	n.-8T>C		upstream_gene_variant		3
AVPR1B	ENST00000612906.1	n.-76A>G		upstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28285 AN: 151924 Hom.: 2877 Cov.: 31

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.0396

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.191

GnomAD4 exome AF: 0.121 AC: 8 AN: 66 Hom.: 1 Cov.: 0 AF XY: 0.104 AC XY: 5 AN XY: 48

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.133 AC: 8 AN: 60

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.186 AC: 28316 AN: 152044 Hom.: 2881 Cov.: 31 AF XY: 0.187 AC XY: 13866 AN XY: 74310

African (AFR) AF: 0.266 AC: 11049 AN: 41462

American (AMR) AF: 0.157 AC: 2400 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 731 AN: 3472

East Asian (EAS) AF: 0.107 AC: 551 AN: 5142

South Asian (SAS) AF: 0.258 AC: 1241 AN: 4808

European-Finnish (FIN) AF: 0.150 AC: 1591 AN: 10602

Middle Eastern (MID) AF: 0.219 AC: 64 AN: 292

European-Non Finnish (NFE) AF: 0.151 AC: 10256 AN: 67948

Other (OTH) AF: 0.188 AC: 397 AN: 2112

Alfa AF: 0.165 Hom.: 3039

Bravo AF: 0.187

Asia WGS AF: 0.195 AC: 679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.8
DANN	Benign	0.49
PhyloP100		-0.36
PromoterAI		0.0041	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs28373064; hg19: chr1-206223556;