Genetic Variant AVPR1B:p.Arg364His (chr1-206110373-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000707.5(AVPR1B):c.1091G>A(p.Arg364His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,609,800 control chromosomes in the GnomAD database, including 11,568 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 0.11 ( 917 hom., cov: 32)

Exomes 𝑓: 0.12 ( 10651 hom. )

Consequence

AVPR1B
NM_000707.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.185

Publications

40 publications found

Variant links:

Genes affected

AVPR1B (HGNC:896): (arginine vasopressin receptor 1B) 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 AVPR1A, V2R and OXT receptors. Its activity is mediated by G proteins which stimulate a phosphatidylinositol-calcium second messenger system. The receptor is primarily located in the anterior pituitary, where it stimulates ACTH release. It is expressed at high levels in ACTH-secreting pituitary adenomas as well as in bronchial carcinoids responsible for the ectopic ACTH syndrome. A spliced antisense transcript of this gene has been reported but its function is not known. [provided by RefSeq, Jul 2008]

AVPR1B links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0032314658).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AVPR1B	NM_000707.5 link	c.1091G>A	p.Arg364His	missense_variant	Exon 2 of 2	ENST00000367126.5	NP_000698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AVPR1B	ENST00000367126.5 link	c.1091G>A	p.Arg364His	missense_variant	Exon 2 of 2	1	NM_000707.5	ENSP00000356094.4
AVPR1B	ENST00000612906.1 link	n.187G>A		non_coding_transcript_exon_variant	Exon 2 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16094

AN:

152072

Hom.:

918

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0916

Gnomad AMI

AF:

0.0253

Gnomad AMR

AF:

0.109

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.101

Gnomad SAS

AF:

0.210

Gnomad FIN

AF:

0.0925

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.109

Gnomad OTH

AF:

0.118

GnomAD2 exomes

AF:

0.125

AC:

29634

AN:

236886

AF XY:

0.130

show subpopulations

Gnomad AFR exome

AF:

0.0933

Gnomad AMR exome

AF:

0.107

Gnomad ASJ exome

AF:

0.117

Gnomad EAS exome

AF:

0.104

Gnomad FIN exome

AF:

0.0986

Gnomad NFE exome

AF:

0.118

Gnomad OTH exome

AF:

0.124

GnomAD4 exome

AF:

0.117

AC:

170911

AN:

1457610

Hom.:

10651

Cov.:

AF XY:

0.121

AC XY:

87638

AN XY:

724948

show subpopulations

African (AFR)

AF:

0.0855

AC:

2857

AN:

33434

American (AMR)

AF:

0.105

AC:

4637

AN:

44028

Ashkenazi Jewish (ASJ)

AF:

0.117

AC:

3039

AN:

26020

East Asian (EAS)

AF:

0.119

AC:

4700

AN:

39566

South Asian (SAS)

AF:

0.212

AC:

18230

AN:

85920

European-Finnish (FIN)

AF:

0.101

AC:

5304

AN:

52418

Middle Eastern (MID)

AF:

0.0980

AC:

564

AN:

5754

European-Non Finnish (NFE)

AF:

0.112

AC:

124585

AN:

1110322

Other (OTH)

AF:

0.116

AC:

6995

AN:

60148

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

10035

20069

30104

40138

50173

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4594

9188

13782

18376

22970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.106

AC:

16099

AN:

152190

Hom.:

917

Cov.:

AF XY:

0.107

AC XY:

7968

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.0915

AC:

3796

AN:

41508

American (AMR)

AF:

0.110

AC:

1677

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.111

AC:

386

AN:

3468

East Asian (EAS)

AF:

0.101

AC:

521

AN:

5174

South Asian (SAS)

AF:

0.210

AC:

1015

AN:

4824

European-Finnish (FIN)

AF:

0.0925

AC:

981

AN:

10600

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.109

AC:

7424

AN:

68002

Other (OTH)

AF:

0.117

AC:

247

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

769

1538

2307

3076

3845

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

190

380

570

760

950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.111

Hom.:

1048

Bravo

AF:

0.104

Asia WGS

AF:

0.167

AC:

583

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_noAF

Benign

-0.47

CADD

Benign

8.8

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.071

LIST_S2

Benign

0.32

MetaRNN

Benign

0.0032

PhyloP100

0.18

PROVEAN

Benign

-0.64

Sift

Benign

0.40

Sift4G

Benign

0.21

Vest4

0.088

gMVP

0.76

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over