chr12-63144678-G-A

Variant names:

• chr12-63144678-G-A
• rs10747983
• NM_000706.5:c.*2681C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

AVPR1A Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000706.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AVPR1A	NM_000706.5	MANE Select	c.*2681C>T		3_prime_UTR	Exon 2 of 2	NP_000697.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AVPR1A	ENST00000299178.4	TSL:1 MANE Select	c.*2681C>T		3_prime_UTR	Exon 2 of 2	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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.556 AC: 23016 AN: 41380

American (AMR) AF: 0.178 AC: 2717 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 734 AN: 3472

East Asian (EAS) AF: 0.150 AC: 775 AN: 5176

South Asian (SAS) AF: 0.326 AC: 1574 AN: 4824

European-Finnish (FIN) AF: 0.148 AC: 1562 AN: 10574

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11771 AN: 67950

Other (OTH) AF: 0.249 AC: 526 AN: 2112

Alfa AF: 0.199 Hom.: 5677

Bravo AF: 0.290

Asia WGS AF: 0.276 AC: 962 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.7
DANN	Benign	0.59
PhyloP100		0.13

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

Other links and lift over

dbSNP: rs10747983; hg19: chr12-63538458;