Genetic Variant NM_004624.4:c.387G>A (chr3-42525981-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004624.4(VIPR1):c.387G>A(p.Ala129Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00303 in 1,611,760 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 70 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 65 hom. )

Consequence

VIPR1
NM_004624.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.57

Publications

2 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: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025151372).

BP6

Variant 3-42525981-G-A is Benign according to our data. Variant chr3-42525981-G-A is described in ClinVar as [Benign]. Clinvar id is 787782.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.57 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VIPR1	NM_004624.4 link	c.387G>A	p.Ala129Ala	synonymous_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.387G>A	p.Ala129Ala	synonymous_variant	Exon 4 of 13	1	NM_004624.4	ENSP00000327246.4		P32241-1

Frequencies

GnomAD3 genomes

AF:

0.0163

AC:

2485

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0557

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00818

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0139

GnomAD2 exomes

AF:

0.00394

AC:

963

AN:

244164

AF XY:

0.00299

show subpopulations

Gnomad AFR exome

AF:

0.0541

Gnomad AMR exome

AF:

0.00247

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000275

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000244

Gnomad OTH exome

AF:

0.00151

GnomAD4 exome

AF:

0.00164

AC:

2393

AN:

1459438

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

1005

AN XY:

725660

show subpopulations

African (AFR)

AF:

0.0542

AC:

1812

AN:

33434

American (AMR)

AF:

0.00349

AC:

155

AN:

44450

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26072

East Asian (EAS)

AF:

0.000151

AC:

AN:

39630

South Asian (SAS)

AF:

0.000164

AC:

AN:

85478

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53202

Middle Eastern (MID)

AF:

0.00226

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000135

AC:

150

AN:

1111090

Other (OTH)

AF:

0.00401

AC:

242

AN:

60320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

118

236

354

472

590

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0163

AC:

2490

AN:

152322

Hom.:

Cov.:

AF XY:

0.0160

AC XY:

1189

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0557

AC:

2316

AN:

41572

American (AMR)

AF:

0.00810

AC:

124

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5172

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

68034

Other (OTH)

AF:

0.0137

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

116

231

347

462

578

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00919

Hom.:

Bravo

AF:

0.0182

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0506

AC:

223

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.00487

AC:

591

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 16, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.40

CADD

Benign

0.086

(source)

DANN

Uncertain

0.99

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0029

LIST_S2

Benign

0.43

MetaRNN

Benign

0.0025

MetaSVM

Benign

-1.0

PhyloP100

-1.6

PROVEAN

Benign

0.69

REVEL

Benign

0.086

Sift

Benign

0.94

Vest4

0.11

MVP

0.12

ClinPred

0.0087

GERP RS

-2.8

Mutation Taster

=100/0

polymorphism (auto)

(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.387G>A

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