rs10747983

Positions:

• chr12-63144678-G-A
• chr12-63144678-G-T

Variant summary

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

The NM_000706.5(AVPR1A):​c.*2681C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 151,980 control chromosomes in the GnomAD database, including 8,404 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 (8404 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AVPR1A NM_000706.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.125

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AVPR1A	NM_000706.5	c.*2681C>T		3_prime_UTR_variant	2/2	ENST00000299178.4	NP_000697.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AVPR1A	ENST00000299178	c.*2681C>T		3_prime_UTR_variant	2/2	1	NM_000706.5	ENSP00000299178.3

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42924 AN: 151860 Hom.: 8381 Cov.: 32

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.252

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.283 AC: 42984 AN: 151980 Hom.: 8404 Cov.: 32 AF XY: 0.279 AC XY: 20738 AN XY: 74328

Gnomad4 AFR AF: 0.556

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.249

Alfa AF: 0.189 Hom.: 3904

Bravo AF: 0.290

Asia WGS AF: 0.276 AC: 962 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.7
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs10747983; hg19: chr12-63538458;