1-206109537-C-T

Variant names:

• chr1-206109537-C-T
• rs35439639
• NM_000707.5:c.*652G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000707.5(AVPR1B):​c.*652G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0166 in 152,046 control chromosomes in the GnomAD database, including 26 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 0.017 (26 hom., cov: 32)
• Consequence: AVPR1B NM_000707.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 1 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0166 (2531/152046) while in subpopulation AFR AF = 0.0209 (866/41458). AF 95% confidence interval is 0.0197. There are 26 homozygotes in GnomAd4. There are 1261 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AVPR1B	NM_000707.5	c.*652G>A		3_prime_UTR_variant	Exon 2 of 2	ENST00000367126.5	NP_000698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AVPR1B	ENST00000367126.5	c.*652G>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_000707.5	ENSP00000356094.4

Frequencies

GnomAD3 genomes AF: 0.0167 AC: 2530 AN: 151928 Hom.: 26 Cov.: 32

Gnomad AFR AF: 0.0209

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0165

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0158

Gnomad FIN AF: 0.0157

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0157

Gnomad OTH AF: 0.0139

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0166 AC: 2531 AN: 152046 Hom.: 26 Cov.: 32 AF XY: 0.0170 AC XY: 1261 AN XY: 74312

African (AFR) AF: 0.0209 AC: 866 AN: 41458

American (AMR) AF: 0.0165 AC: 252 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 70 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.0156 AC: 75 AN: 4808

European-Finnish (FIN) AF: 0.0157 AC: 166 AN: 10568

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0157 AC: 1065 AN: 67986

Other (OTH) AF: 0.0138 AC: 29 AN: 2104

Alfa AF: 0.0162 Hom.: 22

Bravo AF: 0.0160

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.55
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs35439639; hg19: chr1-206231794;