rs2282018

Variant names:

• chr20-3084303-C-T
• rs2282018
• NM_000490.5:c.120+252G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-3084303-C-T
• chr20-3084303-C-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000490.5(AVP):​c.120+252G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 152,030 control chromosomes in the GnomAD database, including 28,267 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.60 (28267 hom., cov: 32)
• Consequence: AVP NM_000490.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.575
• Publications: 14 publications found

Genes affected

AVP (HGNC:894): (arginine vasopressin) This gene encodes a member of the vasopressin/oxytocin family and preproprotein that is proteolytically processed to generate multiple protein products. These products include the neuropeptide hormone arginine vasopressin, and two other peptides, neurophysin 2 and copeptin. Arginine vasopressin is a posterior pituitary hormone that is synthesized in the supraoptic nucleus and paraventricular nucleus of the hypothalamus. Along with its carrier protein, neurophysin 2, it is packaged into neurosecretory vesicles and transported axonally to the nerve endings in the neurohypophysis where it is either stored or secreted into the bloodstream. The precursor is thought to be activated while it is being transported along the axon to the posterior pituitary. Arginine vasopressin acts as a growth factor by enhancing pH regulation through acid-base transport systems. It has a direct antidiuretic action on the kidney, and also causes vasoconstriction of the peripheral vessels. This hormone can contract smooth muscle during parturition and lactation. It is also involved in cognition, tolerance, adaptation and complex sexual and maternal behaviour, as well as in the regulation of water excretion and cardiovascular functions. Mutations in this gene cause autosomal dominant neurohypophyseal diabetes insipidus (ADNDI). This gene is present in a gene cluster with the related gene oxytocin on chromosome 20. [provided by RefSeq, Nov 2015]

AVP Gene-Disease associations (from GenCC):

• neurohypophyseal diabetes insipidus

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 20-3084303-C-T is Benign according to our data. Variant chr20-3084303-C-T is described in ClinVar as Benign. ClinVar VariationId is 1182116.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000490.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AVP	NM_000490.5	MANE Select	c.120+252G>A		intron	N/A	NP_000481.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AVP	ENST00000380293.3	TSL:1 MANE Select	c.120+252G>A		intron	N/A	ENSP00000369647.3	P01185

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91307 AN: 151912 Hom.: 28253 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.597

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

GnomAD4 genome AF: 0.601 AC: 91367 AN: 152030 Hom.: 28267 Cov.: 32 AF XY: 0.606 AC XY: 45064 AN XY: 74306

African (AFR) AF: 0.443 AC: 18342 AN: 41450

American (AMR) AF: 0.710 AC: 10850 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 2071 AN: 3466

East Asian (EAS) AF: 0.646 AC: 3336 AN: 5162

South Asian (SAS) AF: 0.681 AC: 3287 AN: 4826

European-Finnish (FIN) AF: 0.674 AC: 7137 AN: 10588

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.655 AC: 44478 AN: 67944

Other (OTH) AF: 0.601 AC: 1268 AN: 2110

Alfa AF: 0.637 Hom.: 44947

Bravo AF: 0.595

Asia WGS AF: 0.678 AC: 2355 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.6
DANN	Benign	0.79
PhyloP100		-0.57
PromoterAI		0.012	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs2282018; hg19: chr20-3064949;