chr3-42525890-G-A

Variant names:

Variant summary

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

The NM_004624.4(VIPR1):c.296G>A(p.Arg99His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,455,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R99S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

VIPR1
NM_004624.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0680

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]

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=0.14917341).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VIPR1	NM_004624.4 link	c.296G>A	p.Arg99His	missense_variant	Exon 4 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.296G>A	p.Arg99His	missense_variant	Exon 4 of 13	1	NM_004624.4	ENSP00000327246.4		P32241-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000126

AC:

AN:

239014

AF XY:

0.0000155

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000559

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000926

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000117

AC:

AN:

1455924

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

723614

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33392

American (AMR)

AF:

0.00

AC:

AN:

43986

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25972

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39474

South Asian (SAS)

AF:

0.0000707

AC:

AN:

84890

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52654

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000721

AC:

AN:

1109638

Other (OTH)

AF:

0.0000166

AC:

AN:

60158

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 24, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.296G>A (p.R99H) alteration is located in exon 4 (coding exon 4) of the VIPR1 gene. This alteration results from a G to A substitution at nucleotide position 296, causing the arginine (R) at amino acid position 99 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

Benign

0.088

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

7.9

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

.;T;.;.;T

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.53

T;T;T;T;T

M_CAP

Benign

0.039

MetaRNN

Benign

0.15

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

.;.;.;.;L

PhyloP100

0.068

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.68

N;N;N;N;N

REVEL

Benign

0.16

Sift

Benign

0.54

T;T;T;T;T

Sift4G

Benign

0.56

T;T;T;T;T

Polyphen

0.91

.;.;.;.;P

Vest4

0.13

MVP

0.60

MPC

0.11

ClinPred

0.088

GERP RS

-1.6

Varity_R

0.025

gMVP

0.73

Mutation Taster

=95/5

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

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chr3-42525890-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over