Genetic Variant NM_000707.5:c.571G>C (chr1-206116320-C-G) – 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.571G>C(p.Gly191Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0459 in 1,613,466 control chromosomes in the GnomAD database, including 2,137 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.061 ( 355 hom., cov: 32)

Exomes 𝑓: 0.044 ( 1782 hom. )

Consequence

AVPR1B
NM_000707.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.316

Publications

21 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=0.0038514733).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AVPR1B	NM_000707.5 link	c.571G>C	p.Gly191Arg	missense_variant	Exon 1 of 2	ENST00000367126.5	NP_000698.1	P47901

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AVPR1B	ENST00000367126.5 link	c.571G>C	p.Gly191Arg	missense_variant	Exon 1 of 2	1	NM_000707.5	ENSP00000356094.4		P47901
AVPR1B	ENST00000612906.1 link	n.36+1344G>C		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes

AF:

0.0611

AC:

9299

AN:

152130

Hom.:

355

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0992

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0376

Gnomad ASJ

AF:

0.0919

Gnomad EAS

AF:

0.00617

Gnomad SAS

AF:

0.0474

Gnomad FIN

AF:

0.0683

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.0461

Gnomad OTH

AF:

0.0583

GnomAD2 exomes

AF:

0.0500

AC:

12409

AN:

248102

AF XY:

0.0501

show subpopulations

Gnomad AFR exome

AF:

0.103

Gnomad AMR exome

AF:

0.0271

Gnomad ASJ exome

AF:

0.0992

Gnomad EAS exome

AF:

0.00562

Gnomad FIN exome

AF:

0.0609

Gnomad NFE exome

AF:

0.0497

Gnomad OTH exome

AF:

0.0596

GnomAD4 exome

AF:

0.0443

AC:

64753

AN:

1461218

Hom.:

1782

Cov.:

AF XY:

0.0449

AC XY:

32616

AN XY:

726950

show subpopulations

African (AFR)

AF:

0.109

AC:

3636

AN:

33480

American (AMR)

AF:

0.0292

AC:

1307

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0973

AC:

2544

AN:

26136

East Asian (EAS)

AF:

0.00741

AC:

294

AN:

39700

South Asian (SAS)

AF:

0.0522

AC:

4499

AN:

86258

European-Finnish (FIN)

AF:

0.0604

AC:

3188

AN:

52756

Middle Eastern (MID)

AF:

0.107

AC:

620

AN:

5768

European-Non Finnish (NFE)

AF:

0.0410

AC:

45561

AN:

1112006

Other (OTH)

AF:

0.0514

AC:

3104

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

4184

8368

12551

16735

20919

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1664

3328

4992

6656

8320

<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:

0.0612

AC:

9312

AN:

152248

Hom.:

355

Cov.:

AF XY:

0.0609

AC XY:

4531

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0994

AC:

4130

AN:

41540

American (AMR)

AF:

0.0376

AC:

575

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0919

AC:

319

AN:

3472

East Asian (EAS)

AF:

0.00618

AC:

AN:

5174

South Asian (SAS)

AF:

0.0472

AC:

228

AN:

4826

European-Finnish (FIN)

AF:

0.0683

AC:

724

AN:

10596

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0461

AC:

3135

AN:

68016

Other (OTH)

AF:

0.0568

AC:

120

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

455

910

1366

1821

2276

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

216

324

432

540

<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:

0.0433

Hom.:

120

Bravo

AF:

0.0606

Asia WGS

AF:

0.0260

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.036

LIST_S2

Benign

0.31

MetaRNN

Benign

0.0039

PhyloP100

0.32

PROVEAN

Benign

0.81

Sift

Benign

0.30

Sift4G

Benign

0.50

Vest4

0.12

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