7-159030743-G-T

Position:

chr7-159030743-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_003382.5(VIPR2):c.1190C>A(p.Pro397Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000503 in 1,590,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

VIPR2
NM_003382.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00100

Variant links:

Genes affected

VIPR2 (HGNC:12695): (vasoactive intestinal peptide receptor 2) 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. [provided by RefSeq, Aug 2011]

VIPR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.043700308).

BP6

Variant 7-159030743-G-T is Benign according to our data. Variant chr7-159030743-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2261100.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
VIPR2	NM_003382.5 linkuse as main transcript	c.1190C>A	p.Pro397Gln	missense_variant	13/13	ENST00000262178.7	NP_003373.2
VIPR2	NM_001308259.1 linkuse as main transcript	c.1142C>A	p.Pro381Gln	missense_variant	10/10		NP_001295188.1
VIPR2	NM_001304522.2 linkuse as main transcript	c.950C>A	p.Pro317Gln	missense_variant	11/11		NP_001291451.1
VIPR2	NR_130758.2 linkuse as main transcript	n.1620C>A		non_coding_transcript_exon_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VIPR2	ENST00000262178.7 linkuse as main transcript	c.1190C>A	p.Pro397Gln	missense_variant	13/13	1	NM_003382.5	ENSP00000262178	P2	P41587-1
VIPR2	ENST00000402066.5 linkuse as main transcript	c.1613C>A	p.Pro538Gln	missense_variant	13/13	5		ENSP00000384497	A2
VIPR2	ENST00000377633.7 linkuse as main transcript	c.1142C>A	p.Pro381Gln	missense_variant	10/10	2		ENSP00000366860		P41587-2

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000209

AC:

AN:

1437926

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

713358

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000239

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.000121

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000196

Hom.:

Bravo

AF:

0.0000567

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.39

DANN

Benign

0.78

DEOGEN2

Benign

0.063

T;.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.51

T;T;T

M_CAP

Benign

0.0089

MetaRNN

Benign

0.044

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.76

N;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

2.4

N;N;N

REVEL

Benign

0.080

Sift

Benign

0.22

T;T;T

Sift4G

Benign

0.33

T;T;T

Polyphen

0.0020

B;.;.

Vest4

0.071

MVP

0.085

MPC

0.17

ClinPred

0.33

GERP RS

-3.9

Varity_R

0.033

gMVP

0.19

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