Variant 3-42527411-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004624.4(VIPR1):c.418G>C(p.Gly140Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

VIPR1
NM_004624.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.07

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 (HGNC:):

VIPR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.050750047).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VIPR1	NM_004624.4 linkuse as main transcript	c.418G>C	p.Gly140Arg	missense_variant	5/13	ENST00000325123.5	NP_004615.2	P32241-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VIPR1	ENST00000325123.5 linkuse as main transcript	c.418G>C	p.Gly140Arg	missense_variant	5/13	1	NM_004624.4	ENSP00000327246.4		P32241-1

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151670

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251362

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461624

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000937

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151670

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74036

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 26, 2024

The c.418G>C (p.G140R) alteration is located in exon 5 (coding exon 5) of the VIPR1 gene. This alteration results from a G to C substitution at nucleotide position 418, causing the glycine (G) at amino acid position 140 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Benign

-0.38

CADD

Benign

7.7

DANN

Benign

0.78

DEOGEN2

Benign

0.021

.;T;.;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.18

T;T;T;T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.051

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.2

.;.;.;.;L

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.33

N;N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.55

T;T;T;T;T

Sift4G

Benign

0.39

T;T;T;T;T

Polyphen

0.0020

.;.;.;.;B

Vest4

0.20

MutPred

0.55

.;.;.;Gain of catalytic residue at G140 (P = 0.0458);Gain of catalytic residue at G140 (P = 0.0458);

MVP

0.35

MPC

0.16

ClinPred

0.023

GERP RS

-3.8

Varity_R

0.15

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over