Variant chr3-42513831-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_004624.4(VIPR1):c.161C>A(p.Ala54Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00243 in 1,551,556 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 6 hom. )

Consequence

VIPR1
NM_004624.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.722

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005968094).

BS2

High Homozygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VIPR1	NM_004624.4 linkuse as main transcript	c.161C>A	p.Ala54Asp	missense_variant	2/13	ENST00000325123.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VIPR1	ENST00000325123.5 linkuse as main transcript	c.161C>A	p.Ala54Asp	missense_variant	2/13	1	NM_004624.4	P4	P32241-1
VIPR1-AS1	ENST00000452639.7 linkuse as main transcript	n.1008-1539G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00139

AC:

211

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00278

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00118

AC:

185

AN:

156354

Hom.:

AF XY:

0.00106

AC XY:

AN XY:

82244

show subpopulations

Gnomad AFR exome

AF:

0.000114

Gnomad AMR exome

AF:

0.000121

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000390

Gnomad NFE exome

AF:

0.00283

Gnomad OTH exome

AF:

0.000908

GnomAD4 exome

AF:

0.00254

AC:

3554

AN:

1399288

Hom.:

Cov.:

AF XY:

0.00236

AC XY:

1629

AN XY:

690184

show subpopulations

Gnomad4 AFR exome

AF:

0.000190

Gnomad4 AMR exome

AF:

0.000168

Gnomad4 ASJ exome

AF:

0.0000795

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000252

Gnomad4 FIN exome

AF:

0.000609

Gnomad4 NFE exome

AF:

0.00315

Gnomad4 OTH exome

AF:

0.00185

GnomAD4 genome

AF:

0.00139

AC:

211

AN:

152268

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00278

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00244

Hom.:

Bravo

AF:

0.00153

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000484

AC:

ESP6500EA

AF:

0.00213

AC:

ExAC

AF:

0.000624

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2021

The c.161C>A (p.A54D) alteration is located in exon 2 (coding exon 2) of the VIPR1 gene. This alteration results from a C to A substitution at nucleotide position 161, causing the alanine (A) at amino acid position 54 to be replaced by an aspartic acid (D). 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

0.12

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.45

T;T;T;T

M_CAP

Benign

0.0093

MetaRNN

Benign

0.0060

T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.2

N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.22

T;T;T;T

Sift4G

Benign

0.63

T;D;D;T

Polyphen

0.54

.;.;.;P

Vest4

0.20

MVP

0.42

MPC

0.13

ClinPred

0.010

GERP RS

2.3

Varity_R

0.11

gMVP

0.75

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

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