Genetic Variant AVPR1B:p.Lys65Asn (chr1-206116696-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.195G>C(p.Lys65Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0532 in 1,608,580 control chromosomes in the GnomAD database, including 2,676 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 0.040 ( 180 hom., cov: 32)

Exomes 𝑓: 0.055 ( 2496 hom. )

Consequence

AVPR1B
NM_000707.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.39

Publications

38 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=0.049516648).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AVPR1B	NM_000707.5 link	c.195G>C	p.Lys65Asn	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.195G>C	p.Lys65Asn	missense_variant	Exon 1 of 2	1	NM_000707.5	ENSP00000356094.4		P47901
AVPR1B	ENST00000612906.1 link	n.36+968G>C		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes

AF:

0.0401

AC:

6105

AN:

152170

Hom.:

180

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0114

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0415

Gnomad ASJ

AF:

0.0548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00766

Gnomad FIN

AF:

0.0419

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0617

Gnomad OTH

AF:

0.0507

GnomAD2 exomes

AF:

0.0429

AC:

10553

AN:

246128

AF XY:

0.0434

show subpopulations

Gnomad AFR exome

AF:

0.00994

Gnomad AMR exome

AF:

0.0296

Gnomad ASJ exome

AF:

0.0529

Gnomad EAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.0459

Gnomad NFE exome

AF:

0.0663

Gnomad OTH exome

AF:

0.0516

GnomAD4 exome

AF:

0.0546

AC:

79551

AN:

1456292

Hom.:

2496

Cov.:

AF XY:

0.0538

AC XY:

38975

AN XY:

723826

show subpopulations

African (AFR)

AF:

0.00778

AC:

260

AN:

33406

American (AMR)

AF:

0.0304

AC:

1351

AN:

44368

Ashkenazi Jewish (ASJ)

AF:

0.0517

AC:

1325

AN:

25644

East Asian (EAS)

AF:

0.0000757

AC:

AN:

39622

South Asian (SAS)

AF:

0.00785

AC:

671

AN:

85432

European-Finnish (FIN)

AF:

0.0488

AC:

2593

AN:

53114

Middle Eastern (MID)

AF:

0.0250

AC:

143

AN:

5730

European-Non Finnish (NFE)

AF:

0.0633

AC:

70209

AN:

1108836

Other (OTH)

AF:

0.0498

AC:

2996

AN:

60140

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

5105

10210

15316

20421

25526

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2514

5028

7542

10056

12570

<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:

0.0401

AC:

6104

AN:

152288

Hom.:

180

Cov.:

AF XY:

0.0379

AC XY:

2823

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0113

AC:

471

AN:

41560

American (AMR)

AF:

0.0415

AC:

635

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0548

AC:

190

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00787

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0419

AC:

445

AN:

10616

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0618

AC:

4201

AN:

68018

Other (OTH)

AF:

0.0497

AC:

105

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

304

609

913

1218

1522

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<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:

0.0463

Hom.:

Bravo

AF:

0.0392

Asia WGS

AF:

0.00635

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_noAF

Pathogenic

0.24

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

LIST_S2

Benign

0.71

MetaRNN

Benign

0.050

PhyloP100

1.4

PROVEAN

Uncertain

-4.1

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.025

Vest4

0.68

gMVP

0.97

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