3-42502740-G-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_004624.4(VIPR1):​c.5G>A​(p.Arg2His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000281 in 1,317,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

VIPR1
NM_004624.4 missense

Scores

2
4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.55

Publications

1 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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.1834833).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VIPR1NM_004624.4 linkc.5G>A p.Arg2His missense_variant Exon 1 of 13 ENST00000325123.5 NP_004615.2 P32241-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
VIPR1ENST00000325123.5 linkc.5G>A p.Arg2His missense_variant Exon 1 of 13 1 NM_004624.4 ENSP00000327246.4 P32241-1

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152004
Hom.:
0
Cov.:
33
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:
0.000388
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00
AC:
0
AN:
19672
AF XY:
0.00
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 FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000300
AC:
35
AN:
1165934
Hom.:
0
Cov.:
31
AF XY:
0.0000300
AC XY:
17
AN XY:
566154
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
23530
American (AMR)
AF:
0.00
AC:
0
AN:
11700
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
16768
East Asian (EAS)
AF:
0.000778
AC:
21
AN:
26986
South Asian (SAS)
AF:
0.00
AC:
0
AN:
42080
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
25848
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3192
European-Non Finnish (NFE)
AF:
0.00000103
AC:
1
AN:
968940
Other (OTH)
AF:
0.000277
AC:
13
AN:
46890
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.478
Heterozygous variant carriers
0
2
4
6
8
10
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.0000132
AC:
2
AN:
152004
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74254
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41420
American (AMR)
AF:
0.00
AC:
0
AN:
15266
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.000388
AC:
2
AN:
5152
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10576
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67976
Other (OTH)
AF:
0.00
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.000142
Hom.:
0
Bravo
AF:
0.0000529
Asia WGS
AF:
0.000873
AC:
3
AN:
3450

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 08, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.5G>A (p.R2H) alteration is located in exon 1 (coding exon 1) of the VIPR1 gene. This alteration results from a G to A substitution at nucleotide position 5, causing the arginine (R) at amino acid position 2 to be replaced by a histidine (H). 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
Uncertain
0.39
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
18
DANN
Benign
0.95
DEOGEN2
Benign
0.17
.;T
Eigen
Benign
-0.68
Eigen_PC
Benign
-0.61
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.51
T;T
M_CAP
Pathogenic
0.37
D
MetaRNN
Benign
0.18
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.81
.;L
PhyloP100
1.6
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-0.68
N;N
REVEL
Benign
0.055
Sift
Uncertain
0.0030
D;T
Sift4G
Uncertain
0.033
D;D
Polyphen
0.0010
.;B
Vest4
0.22
MutPred
0.28
Loss of glycosylation at P6 (P = 0.0026);Loss of glycosylation at P6 (P = 0.0026);
MVP
0.43
MPC
0.27
ClinPred
0.44
T
GERP RS
1.8
PromoterAI
0.0030
Neutral
Varity_R
0.034
gMVP
0.37
Mutation Taster
=296/4
polymorphism

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

Other links and lift over

dbSNP: rs371174986; hg19: chr3-42544232; API