Genetic Variant VIPR1:p.Val159Val (chr3-42527470-C-T) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_004624.4(VIPR1):c.477C>T(p.Val159Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,613,896 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0028 ( 32 hom. )

Consequence

VIPR1
NM_004624.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.04

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 3-42527470-C-T is Benign according to our data. Variant chr3-42527470-C-T is described in ClinVar as Benign. ClinVar VariationId is 733479.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.04 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004624.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VIPR1	NM_004624.4	MANE Select	c.477C>T	p.Val159Val	synonymous	Exon 5 of 13	NP_004615.2
VIPR1	NM_001251885.2		c.396C>T	p.Val132Val	synonymous	Exon 5 of 13	NP_001238814.1	B4DNY6
VIPR1	NM_001251882.2		c.354C>T	p.Val118Val	synonymous	Exon 6 of 14	NP_001238811.1	P32241-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VIPR1	ENST00000325123.5	TSL:1 MANE Select	c.477C>T	p.Val159Val	synonymous	Exon 5 of 13	ENSP00000327246.4	P32241-1
VIPR1	ENST00000883021.1		c.507C>T	p.Val169Val	synonymous	Exon 5 of 13	ENSP00000553080.1
VIPR1	ENST00000883016.1		c.474C>T	p.Val158Val	synonymous	Exon 5 of 13	ENSP00000553075.1

Frequencies

GnomAD3 genomes

AF:

0.00250

AC:

381

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.0375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00213

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00342

AC:

860

AN:

251268

AF XY:

0.00338

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.0483

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000977

Gnomad NFE exome

AF:

0.00228

Gnomad OTH exome

AF:

0.00456

GnomAD4 exome

AF:

0.00279

AC:

4082

AN:

1461602

Hom.:

Cov.:

AF XY:

0.00281

AC XY:

2043

AN XY:

727132

show subpopulations

African (AFR)

AF:

0.000568

AC:

AN:

33480

American (AMR)

AF:

0.00105

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.0462

AC:

1206

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00112

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.000883

AC:

AN:

53240

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00215

AC:

2388

AN:

1111942

Other (OTH)

AF:

0.00457

AC:

276

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

212

424

635

847

1059

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

220

330

440

550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00250

AC:

381

AN:

152294

Hom.:

Cov.:

AF XY:

0.00252

AC XY:

188

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.000577

AC:

AN:

41562

American (AMR)

AF:

0.00411

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0375

AC:

130

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00213

AC:

145

AN:

68018

Other (OTH)

AF:

0.00237

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00507

Hom.:

Bravo

AF:

0.00235

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00294

EpiControl

AF:

0.00243

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.45

(source)

DANN

Benign

0.86

PhyloP100

-2.0

Mutation Taster

=98/2

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over