7-159096904-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_003382.5(VIPR2):c.357+6853C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00091 in 1,550,550 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0030 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00068 (14 hom.)
• Consequence: VIPR2 NM_003382.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.26

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 7-159096904-G-A is Benign according to our data. Variant chr7-159096904-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2658286.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VIPR2	NM_003382.5	c.357+6853C>T		intron_variant		ENST00000262178.7
VIPR2	NM_001308259.1	c.240C>T	p.Asn80=	synonymous_variant	1/10
VIPR2	NM_001304522.2	c.357+6853C>T		intron_variant
VIPR2	NR_130758.2	n.453+6853C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VIPR2	ENST00000262178.7	c.357+6853C>T		intron_variant		1	NM_003382.5	P2
VIPR2	ENST00000377633.7	c.240C>T	p.Asn80=	synonymous_variant	1/10	2
VIPR2	ENST00000402066.5	c.780+6853C>T		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.00299 AC: 455 AN: 152112 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00951

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00934

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000960

GnomAD3 exomes AF: 0.00172 AC: 258 AN: 149888 Hom.: 6 AF XY: 0.00196 AC XY: 158 AN XY: 80688

Gnomad AFR exome AF: 0.0115

Gnomad AMR exome AF: 0.000488

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00724

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000360

Gnomad OTH exome AF: 0.000461

GnomAD4 exome AF: 0.000684 AC: 956 AN: 1398320 Hom.: 14 Cov.: 31 AF XY: 0.000848 AC XY: 585 AN XY: 689698

Gnomad4 AFR exome AF: 0.00842

Gnomad4 AMR exome AF: 0.000532

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.00732

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000250

Gnomad4 OTH exome AF: 0.00103

GnomAD4 genome AF: 0.00299 AC: 455 AN: 152230 Hom.: 1 Cov.: 33 AF XY: 0.00314 AC XY: 234 AN XY: 74434

Gnomad4 AFR AF: 0.00948

Gnomad4 AMR AF: 0.000719

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00934

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.000950

Alfa AF: 0.000900 Hom.: 0

Bravo AF: 0.00315

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2022

VIPR2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.32
Dann	Benign	0.48

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: rs533811103; hg19: chr7-158889595; COSMIC: COSV51103117;