Genetic Variant VIPR1:p.Arg78Pro (chr3-42519271-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004624.4(VIPR1):c.233G>C(p.Arg78Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,458,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R78Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

VIPR1
NM_004624.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00300

Publications

0 publications found

Variant links:

Genes affected

VIPR1 (HGNC:12694): (vasoactive intestinal peptide receptor 1) This gene encodes a receptor for vasoactive intestinal peptide, a small neuropeptide. Vasoactive intestinal peptide is involved in smooth muscle relaxation, exocrine and endocrine secretion, and water and ion flux in lung and intestinal epithelia. Its actions are effected through integral membrane receptors associated with a guanine nucleotide binding protein which activates adenylate cyclase. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

VIPR1 links:

VIPR1-AS1 (HGNC:40610): (VIPR1 antisense RNA 1)

VIPR1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09496805).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VIPR1	NM_004624.4 link	c.233G>C	p.Arg78Pro	missense_variant	Exon 3 of 13	ENST00000325123.5	NP_004615.2	P32241-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VIPR1	ENST00000325123.5 link	c.233G>C	p.Arg78Pro	missense_variant	Exon 3 of 13	1	NM_004624.4	ENSP00000327246.4		P32241-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1458378

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

725338

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33356

American (AMR)

AF:

0.00

AC:

AN:

44224

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26080

East Asian (EAS)

AF:

0.00

AC:

AN:

39378

South Asian (SAS)

AF:

0.00

AC:

AN:

85410

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0000144

AC:

AN:

1110508

Other (OTH)

AF:

0.00

AC:

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.016

.;T;.;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.57

T;T;T;T;T

M_CAP

Benign

0.0095

MetaRNN

Benign

0.095

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.77

.;.;.;.;N

PhyloP100

0.0030

PrimateAI

Benign

0.43

PROVEAN

Benign

0.23

N;N;N;N;N

REVEL

Benign

0.081

Sift

Benign

0.17

T;D;T;T;T

Sift4G

Benign

0.15

T;T;T;T;T

Polyphen

0.0040

.;.;.;.;B

Vest4

0.17

MutPred

0.47

.;.;.;Gain of catalytic residue at P77 (P = 0.0119);Gain of catalytic residue at P77 (P = 0.0119);

MVP

0.30

MPC

0.13

ClinPred

0.32

GERP RS

0.67

Varity_R

0.13

gMVP

0.85

Mutation Taster

=76/24

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

3-42519271-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over