Variant 3-42525889-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_004624.4(VIPR1):c.295C>A(p.Arg99Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00303 in 1,608,186 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 9 hom. )

Consequence

VIPR1
NM_004624.4 missense, splice_region

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0360

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP6

Variant 3-42525889-C-A is Benign according to our data. Variant chr3-42525889-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 785794.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VIPR1	NM_004624.4 linkuse as main transcript	c.295C>A	p.Arg99Ser	missense_variant, splice_region_variant	4/13	ENST00000325123.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VIPR1	ENST00000325123.5 linkuse as main transcript	c.295C>A	p.Arg99Ser	missense_variant, splice_region_variant	4/13	1	NM_004624.4	P4	P32241-1
VIPR1-AS1	ENST00000452639.7 linkuse as main transcript	n.952+2660G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00194

AC:

295

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000849

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00366

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00212

AC:

507

AN:

238796

Hom.:

AF XY:

0.00208

AC XY:

269

AN XY:

129100

show subpopulations

Gnomad AFR exome

AF:

0.000998

Gnomad AMR exome

AF:

0.000446

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000241

Gnomad FIN exome

AF:

0.00132

Gnomad NFE exome

AF:

0.00402

Gnomad OTH exome

AF:

0.00188

GnomAD4 exome

AF:

0.00315

AC:

4583

AN:

1455882

Hom.:

Cov.:

AF XY:

0.00309

AC XY:

2237

AN XY:

723534

show subpopulations

Gnomad4 AFR exome

AF:

0.000509

Gnomad4 AMR exome

AF:

0.000545

Gnomad4 ASJ exome

AF:

0.0000385

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000259

Gnomad4 FIN exome

AF:

0.00116

Gnomad4 NFE exome

AF:

0.00391

Gnomad4 OTH exome

AF:

0.00183

GnomAD4 genome

AF:

0.00194

AC:

295

AN:

152304

Hom.:

Cov.:

AF XY:

0.00175

AC XY:

130

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000849

Gnomad4 NFE

AF:

0.00366

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00286

Hom.:

Bravo

AF:

0.00204

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00291

AC:

ExAC

AF:

0.00227

AC:

276

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Feb 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.37

Cadd

Benign

Dann

Benign

0.83

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.45

T;T;T;T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.0076

T;T;T;T;T

MetaSVM

Benign

-0.94

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

0.27

N;N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.40

T;T;T;T;T

Sift4G

Benign

0.55

T;T;T;T;T

Polyphen

0.0070

.;.;.;.;B

Vest4

0.25

MVP

0.49

MPC

0.11

ClinPred

0.0045

GERP RS

2.0

Varity_R

0.095

gMVP

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.39

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.39

Position offset: 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