NM_000706.5:c.-242C>T

Variant names:

• chr12-63151078-G-A
• rs3741865
• NM_000706.5:c.-242C>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.-242C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0211 in 517,080 control chromosomes in the GnomAD database, including 594 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 0.016 (105 hom., cov: 32)
  • Exomes 𝑓: 0.023 (489 hom.)
• Consequence: AVPR1A NM_000706.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634
• Publications: 9 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

ENSG00000279444 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.146 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.-242C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	NP_000697.1
	AVPR1A	NM_000706.5	MANE Select	c.-242C>T		5_prime_UTR	Exon 1 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.-242C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000299178.3
	AVPR1A	ENST00000299178.4	TSL:1 MANE Select	c.-242C>T		5_prime_UTR	Exon 1 of 2	ENSP00000299178.3
	ENSG00000279444	ENST00000624438.1	TSL:5	n.14G>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.0159 AC: 2409 AN: 151968 Hom.: 105 Cov.: 32

Gnomad AFR AF: 0.0100

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.0141

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.00666

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.0233 AC: 8519 AN: 364994 Hom.: 489 Cov.: 5 AF XY: 0.0267 AC XY: 4991 AN XY: 187242

African (AFR) AF: 0.00853 AC: 79 AN: 9266

American (AMR) AF: 0.00279 AC: 32 AN: 11456

Ashkenazi Jewish (ASJ) AF: 0.00292 AC: 32 AN: 10970

East Asian (EAS) AF: 0.123 AC: 3063 AN: 24892

South Asian (SAS) AF: 0.126 AC: 3087 AN: 24498

European-Finnish (FIN) AF: 0.0163 AC: 398 AN: 24426

Middle Eastern (MID) AF: 0.0120 AC: 19 AN: 1580

European-Non Finnish (NFE) AF: 0.00598 AC: 1413 AN: 236406

Other (OTH) AF: 0.0184 AC: 396 AN: 21500

GnomAD4 genome AF: 0.0158 AC: 2402 AN: 152086 Hom.: 105 Cov.: 32 AF XY: 0.0185 AC XY: 1373 AN XY: 74340

African (AFR) AF: 0.0100 AC: 415 AN: 41502

American (AMR) AF: 0.00248 AC: 38 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3468

East Asian (EAS) AF: 0.110 AC: 566 AN: 5124

South Asian (SAS) AF: 0.155 AC: 743 AN: 4802

European-Finnish (FIN) AF: 0.0141 AC: 149 AN: 10596

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.00666 AC: 453 AN: 67984

Other (OTH) AF: 0.0109 AC: 23 AN: 2110

Alfa AF: 0.00641 Hom.: 5

Bravo AF: 0.0120

Asia WGS AF: 0.135 AC: 472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.12
DANN	Benign	0.76
PhyloP100		-0.63
PromoterAI		0.0088	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3741865; hg19: chr12-63544858;