chr12-63150429-A-G

Variant names:

• chr12-63150429-A-G
• rs1042615
• NM_000706.5:c.408T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_000706.5(AVPR1A):​c.408T>C​(p.Phe136Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 1,612,908 control chromosomes in the GnomAD database, including 282,406 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.65 (33256 hom., cov: 34)
  • Exomes 𝑓: 0.58 (249150 hom.)
• Consequence: AVPR1A NM_000706.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.93
• Publications: 58 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

ENSG00000302777 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 12-63150429-A-G is Benign according to our data. Variant chr12-63150429-A-G is described in ClinVar as Benign. ClinVar VariationId is 3060712.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=2.93 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AVPR1A	NM_000706.5	c.408T>C	p.Phe136Phe	synonymous_variant	Exon 1 of 2	ENST00000299178.4	NP_000697.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AVPR1A	ENST00000299178.4	c.408T>C	p.Phe136Phe	synonymous_variant	Exon 1 of 2	1	NM_000706.5	ENSP00000299178.3
AVPR1A	ENST00000550940.1	c.-250T>C		upstream_gene_variant		3		ENSP00000449822.1
ENSG00000302777	ENST00000789494.1	n.-115A>G		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98958 AN: 152054 Hom.: 33210 Cov.: 34

Gnomad AFR AF: 0.831

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.668

GnomAD2 exomes AF: 0.604 AC: 149460 AN: 247436 AF XY: 0.603

Gnomad AFR exome AF: 0.834

Gnomad AMR exome AF: 0.605

Gnomad ASJ exome AF: 0.691

Gnomad EAS exome AF: 0.449

Gnomad FIN exome AF: 0.575

Gnomad NFE exome AF: 0.570

Gnomad OTH exome AF: 0.612

GnomAD4 exome AF: 0.581 AC: 848579 AN: 1460734 Hom.: 249150 Cov.: 88 AF XY: 0.583 AC XY: 423812 AN XY: 726642

African (AFR) AF: 0.837 AC: 28021 AN: 33470

American (AMR) AF: 0.610 AC: 27180 AN: 44578

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 17919 AN: 26110

East Asian (EAS) AF: 0.496 AC: 19684 AN: 39672

South Asian (SAS) AF: 0.689 AC: 59424 AN: 86238

European-Finnish (FIN) AF: 0.582 AC: 30851 AN: 53030

Middle Eastern (MID) AF: 0.696 AC: 4012 AN: 5768

European-Non Finnish (NFE) AF: 0.562 AC: 624741 AN: 1111514

Other (OTH) AF: 0.609 AC: 36747 AN: 60354

GnomAD4 genome AF: 0.651 AC: 99060 AN: 152174 Hom.: 33256 Cov.: 34 AF XY: 0.651 AC XY: 48460 AN XY: 74384

African (AFR) AF: 0.831 AC: 34526 AN: 41564

American (AMR) AF: 0.631 AC: 9655 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2378 AN: 3470

East Asian (EAS) AF: 0.451 AC: 2316 AN: 5132

South Asian (SAS) AF: 0.691 AC: 3334 AN: 4826

European-Finnish (FIN) AF: 0.583 AC: 6181 AN: 10606

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.567 AC: 38561 AN: 67966

Other (OTH) AF: 0.663 AC: 1400 AN: 2112

Alfa AF: 0.586 Hom.: 26971

Bravo AF: 0.657

Asia WGS AF: 0.593 AC: 2062 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

AVPR1A-related disorder Benign:1

Feb 22, 2022

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.7
DANN	Benign	0.91
PhyloP100		2.9
PromoterAI		-0.0041	Neutral
Mutation Taster		=99/1	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: rs1042615; hg19: chr12-63544209; COSMIC: COSV54545532; COSMIC: COSV54545532;