Variant chr12-63149913-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000706.5(AVPR1A):c.924C>A(p.Phe308Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0104 in 1,613,744 control chromosomes in the GnomAD database, including 136 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0082 ( 8 hom., cov: 31)

Exomes 𝑓: 0.011 ( 128 hom. )

Consequence

AVPR1A
NM_000706.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.84

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010125756).

BP6

Variant 12-63149913-G-T is Benign according to our data. Variant chr12-63149913-G-T is described in ClinVar as [Benign]. Clinvar id is 701887.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AVPR1A	NM_000706.5 linkuse as main transcript	c.924C>A	p.Phe308Leu	missense_variant	1/2	ENST00000299178.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AVPR1A	ENST00000299178.4 linkuse as main transcript	c.924C>A	p.Phe308Leu	missense_variant	1/2	1	NM_000706.5	P1
AVPR1A	ENST00000550940.1 linkuse as main transcript	c.267C>A	p.Phe89Leu	missense_variant	1/3	3

Frequencies

GnomAD3 genomes

AF:

0.00821

AC:

1246

AN:

151760

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00182

Gnomad AMI

AF:

0.0165

Gnomad AMR

AF:

0.00447

Gnomad ASJ

AF:

0.0110

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.0100

Gnomad FIN

AF:

0.00948

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0131

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00892

AC:

2242

AN:

251404

Hom.:

AF XY:

0.00987

AC XY:

1341

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00301

Gnomad ASJ exome

AF:

0.00834

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0108

Gnomad FIN exome

AF:

0.0108

Gnomad NFE exome

AF:

0.0124

Gnomad OTH exome

AF:

0.00929

GnomAD4 exome

AF:

0.0107

AC:

15591

AN:

1461866

Hom.:

128

Cov.:

AF XY:

0.0109

AC XY:

7915

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00218

Gnomad4 AMR exome

AF:

0.00324

Gnomad4 ASJ exome

AF:

0.00861

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0115

Gnomad4 FIN exome

AF:

0.0110

Gnomad4 NFE exome

AF:

0.0116

Gnomad4 OTH exome

AF:

0.0112

GnomAD4 genome

AF:

0.00820

AC:

1246

AN:

151878

Hom.:

Cov.:

AF XY:

0.00809

AC XY:

601

AN XY:

74244

show subpopulations

Gnomad4 AFR

AF:

0.00181

Gnomad4 AMR

AF:

0.00446

Gnomad4 ASJ

AF:

0.0110

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.0100

Gnomad4 FIN

AF:

0.00948

Gnomad4 NFE

AF:

0.0131

Gnomad4 OTH

AF:

0.00522

Alfa

AF:

0.00989

Hom.:

Bravo

AF:

0.00691

TwinsUK

AF:

0.0116

AC:

ALSPAC

AF:

0.0109

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.0149

AC:

128

ExAC

AF:

0.00976

AC:

1185

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0108

EpiControl

AF:

0.0101

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.61

D;.

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.98

D;D

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-0.59

MutationAssessor

Pathogenic

4.2

H;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.60

PROVEAN

Pathogenic

-5.6

D;D

REVEL

Uncertain

0.29

Sift

Uncertain

0.0010

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.97

D;.

Vest4

0.66

MutPred

0.72

Gain of catalytic residue at W304 (P = 0);.;

MVP

0.79

MPC

1.7

ClinPred

0.060

GERP RS

2.7

Varity_R

0.78

gMVP

0.81

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over