chr1-206116919-A-G

Variant names:

• chr1-206116919-A-G
• rs35608965
• NM_000707.5:c.-29T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.87).
• 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 rank	MANE	Protein	UniProt
AVPR1B	NM_000707.5	c.-29T>C		5_prime_UTR_variant	Exon 1 of 2	ENST00000367126.5	NP_000698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AVPR1B	ENST00000367126.5	c.-29T>C		5_prime_UTR_variant	Exon 1 of 2	1	NM_000707.5	ENSP00000356094.4
AVPR1B	ENST00000612906.1	n.36+745T>C		intron_variant	Intron 1 of 1	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

GnomAD2 exomes AF: 0.0490 AC: 10979 AN: 224204 AF XY: 0.0493

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 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

African (AFR) AF: 0.109 AC: 3564 AN: 32732

American (AMR) AF: 0.0288 AC: 1196 AN: 41552

Ashkenazi Jewish (ASJ) AF: 0.0951 AC: 2249 AN: 23644

East Asian (EAS) AF: 0.00747 AC: 294 AN: 39354

South Asian (SAS) AF: 0.0515 AC: 4175 AN: 81012

European-Finnish (FIN) AF: 0.0601 AC: 3123 AN: 51940

Middle Eastern (MID) AF: 0.108 AC: 602 AN: 5584

European-Non Finnish (NFE) AF: 0.0408 AC: 44403 AN: 1087432

Other (OTH) AF: 0.0508 AC: 2988 AN: 58802

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

African (AFR) AF: 0.0993 AC: 4123 AN: 41508

American (AMR) AF: 0.0376 AC: 575 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0919 AC: 319 AN: 3470

East Asian (EAS) AF: 0.00619 AC: 32 AN: 5172

South Asian (SAS) AF: 0.0474 AC: 228 AN: 4814

European-Finnish (FIN) AF: 0.0680 AC: 721 AN: 10608

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0461 AC: 3134 AN: 67970

Other (OTH) AF: 0.0575 AC: 121 AN: 2106

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
PhyloP100		-0.060
PromoterAI		-0.0014	Neutral

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

dbSNP: rs35608965; hg19: chr1-206224412;