7-159032034-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_003382.5(VIPR2):c.1005G>A(p.Pro335=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00634 in 1,614,058 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0036 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0066 (47 hom.)
• Consequence: VIPR2 NM_003382.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -7.20

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 7-159032034-C-T is Benign according to our data. Variant chr7-159032034-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 710208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-7.2 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VIPR2	NM_003382.5	c.1005G>A	p.Pro335=	synonymous_variant	11/13	ENST00000262178.7
VIPR2	NM_001308259.1	c.957G>A	p.Pro319=	synonymous_variant	8/10
VIPR2	NM_001304522.2	c.765G>A	p.Pro255=	synonymous_variant	9/11
VIPR2	NR_130758.2	n.1101G>A		non_coding_transcript_exon_variant	11/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VIPR2	ENST00000262178.7	c.1005G>A	p.Pro335=	synonymous_variant	11/13	1	NM_003382.5	P2
VIPR2	ENST00000402066.5	c.1428G>A	p.Pro476=	synonymous_variant	11/13	5		A2
VIPR2	ENST00000377633.7	c.957G>A	p.Pro319=	synonymous_variant	8/10	2

Frequencies

GnomAD3 genomes AF: 0.00364 AC: 554 AN: 152162 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00147

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00353

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00603

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00391 AC: 981 AN: 251146 Hom.: 6 AF XY: 0.00408 AC XY: 554 AN XY: 135842

Gnomad AFR exome AF: 0.00154

Gnomad AMR exome AF: 0.00428

Gnomad ASJ exome AF: 0.00288

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00134

Gnomad FIN exome AF: 0.000739

Gnomad NFE exome AF: 0.00611

Gnomad OTH exome AF: 0.00474

GnomAD4 exome AF: 0.00662 AC: 9675 AN: 1461778 Hom.: 47 Cov.: 32 AF XY: 0.00651 AC XY: 4731 AN XY: 727182

Gnomad4 AFR exome AF: 0.00116

Gnomad4 AMR exome AF: 0.00396

Gnomad4 ASJ exome AF: 0.00245

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00141

Gnomad4 FIN exome AF: 0.000675

Gnomad4 NFE exome AF: 0.00793

Gnomad4 OTH exome AF: 0.00661

GnomAD4 genome AF: 0.00364 AC: 554 AN: 152280 Hom.: 3 Cov.: 33 AF XY: 0.00321 AC XY: 239 AN XY: 74464

Gnomad4 AFR AF: 0.00147

Gnomad4 AMR AF: 0.00353

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00603

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00463 Hom.: 1

Bravo AF: 0.00416

EpiCase AF: 0.00649

EpiControl AF: 0.00670

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	VIPR2: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	0.24
Dann	Benign	0.91

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

Other links and lift over

dbSNP: rs142898881; hg19: chr7-158824725; COSMIC: COSV51103409; COSMIC: COSV51103409;