NM_000707.5:c.195G>C

Variant names:

• chr1-206116696-C-G
• rs35369693
• NM_000707.5:c.195G>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.040 (180 hom., cov: 32)
  • Exomes 𝑓: 0.055 (2496 hom.)
• Consequence: AVPR1B NM_000707.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39

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]

ACMG classification

Verdict is Benign. Variant got -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	c.195G>C	p.Lys65Asn	missense_variant	Exon 1 of 2	ENST00000367126.5	NP_000698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AVPR1B	ENST00000367126.5	c.195G>C	p.Lys65Asn	missense_variant	Exon 1 of 2	1	NM_000707.5	ENSP00000356094.4
AVPR1B	ENST00000612906.1	n.36+968G>C		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes AF: 0.0401 AC: 6105 AN: 152170 Hom.: 180 Cov.: 32

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

GnomAD3 exomes AF: 0.0429 AC: 10553 AN: 246128 Hom.: 321 AF XY: 0.0434 AC XY: 5766 AN XY: 132824

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 SAS exome AF: 0.00770

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.: 34 AF XY: 0.0538 AC XY: 38975 AN XY: 723826

Gnomad4 AFR exome AF: 0.00778

Gnomad4 AMR exome AF: 0.0304

Gnomad4 ASJ exome AF: 0.0517

Gnomad4 EAS exome AF: 0.0000757

Gnomad4 SAS exome AF: 0.00785

Gnomad4 FIN exome AF: 0.0488

Gnomad4 NFE exome AF: 0.0633

Gnomad4 OTH exome AF: 0.0498

GnomAD4 genome AF: 0.0401 AC: 6104 AN: 152288 Hom.: 180 Cov.: 32 AF XY: 0.0379 AC XY: 2823 AN XY: 74468

Gnomad4 AFR AF: 0.0113

Gnomad4 AMR AF: 0.0415

Gnomad4 ASJ AF: 0.0548

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00787

Gnomad4 FIN AF: 0.0419

Gnomad4 NFE AF: 0.0618

Gnomad4 OTH AF: 0.0497

Alfa AF: 0.0463 Hom.: 74

Bravo AF: 0.0392

Asia WGS AF: 0.00635 AC: 23 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	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
LIST_S2	Benign	0.71	T
MetaRNN	Benign	0.050	T
PROVEAN	Uncertain	-4.1	D
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.025	D
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

LitVar

Other links and lift over

dbSNP: rs35369693; hg19: chr1-206224635; COSMIC: COSV65638000; COSMIC: COSV65638000;