12-63144866-G-C

Variant summary

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

The NM_000706.5(AVPR1A):c.*2493C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,810 control chromosomes in the GnomAD database, including 8,035 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 0.28 (8028 hom., cov: 32)
  • Exomes 𝑓: 0.13 (7 hom.)
• Consequence: AVPR1A NM_000706.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.556

Genes affected

AVPR1A (HGNC:895): (arginine vasopressin receptor 1A) 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 AVPR1B, V2R and OXT receptors. Its activity is mediated by G proteins which stimulate a phosphatidylinositol-calcium second messenger system. The receptor mediates cell contraction and proliferation, platelet aggregation, release of coagulation factor and glycogenolysis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AVPR1A	NM_000706.5	c.*2493C>G		3_prime_UTR_variant	2/2	ENST00000299178.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AVPR1A	ENST00000299178.4	c.*2493C>G		3_prime_UTR_variant	2/2	1	NM_000706.5	P1

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42193 AN: 151932 Hom.: 8006 Cov.: 32

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.250

GnomAD4 exome AF: 0.134 AC: 102 AN: 760 Hom.: 7 Cov.: 0 AF XY: 0.158 AC XY: 63 AN XY: 400

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.0952

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.111

Gnomad4 SAS exome AF: 0.250

Gnomad4 NFE exome AF: 0.137

Gnomad4 OTH exome AF: 0.154

GnomAD4 genome AF: 0.278 AC: 42252 AN: 152050 Hom.: 8028 Cov.: 32 AF XY: 0.274 AC XY: 20354 AN XY: 74318

Gnomad4 AFR AF: 0.539

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.247

Alfa AF: 0.120 Hom.: 248

Bravo AF: 0.284

Asia WGS AF: 0.274 AC: 956 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.56
Dann	Benign	0.58

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: rs10784339; hg19: chr12-63538646;