Genetic Variant NM_004624.4:c.266T>C (chr3-42519304-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_004624.4(VIPR1):c.266T>C(p.Ile89Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000882 in 1,609,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000088 ( 0 hom. )

Consequence

VIPR1
NM_004624.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.59

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: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05663219).

BP6

Variant 3-42519304-T-C is Benign according to our data. Variant chr3-42519304-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 765342.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VIPR1	NM_004624.4 link	c.266T>C	p.Ile89Thr	missense_variant	Exon 3 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.266T>C	p.Ile89Thr	missense_variant	Exon 3 of 13	1	NM_004624.4	ENSP00000327246.4		P32241-1

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000150

AC:

AN:

246836

AF XY:

0.000135

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00250

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000800

Gnomad OTH exome

AF:

0.000505

GnomAD4 exome

AF:

0.0000885

AC:

129

AN:

1457750

Hom.:

Cov.:

AF XY:

0.0000869

AC XY:

AN XY:

725000

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33348

American (AMR)

AF:

0.00

AC:

AN:

44162

Ashkenazi Jewish (ASJ)

AF:

0.00318

AC:

AN:

26064

East Asian (EAS)

AF:

0.00

AC:

AN:

39342

South Asian (SAS)

AF:

0.00

AC:

AN:

85258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53374

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0000243

AC:

AN:

1110174

Other (OTH)

AF:

0.000315

AC:

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41450

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000239

Hom.:

Bravo

AF:

0.000121

ExAC

AF:

0.0000988

AC:

EpiCase

AF:

0.000111

EpiControl

AF:

0.0000602

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 15, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.62

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.089

.;T;.;.;T

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.85

D;D;D;D;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.057

T;T;T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.2

.;.;.;.;M

PhyloP100

1.6

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-2.0

N;D;N;D;N

REVEL

Benign

0.18

Sift

Benign

0.057

T;D;T;D;T

Sift4G

Benign

0.10

T;D;T;D;D

Polyphen

0.89

.;.;.;.;P

Vest4

0.67

MutPred

0.60

.;.;.;Loss of stability (P = 0.0078);Loss of stability (P = 0.0078);

MVP

0.73

MPC

0.50

ClinPred

0.11

GERP RS

3.6

Varity_R

0.10

gMVP

0.72

Mutation Taster

=82/18

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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NM_004624.4:c.266T>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over