3-42525981-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_004624.4(VIPR1):c.387G>A(p.Ala129=) 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.57

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-AS1 (HGNC:40610): (VIPR1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -15 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_single_submitter, 1 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/exons	MANE	UniProt
VIPR1	NM_004624.4	c.387G>A	p.Ala129=	synonymous_variant	4/13	ENST00000325123.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VIPR1	ENST00000325123.5	c.387G>A	p.Ala129=	synonymous_variant	4/13	1	NM_004624.4	P4
VIPR1-AS1	ENST00000452639.7	n.952+2568C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0163 AC: 2485 AN: 152204 Hom.: 70 Cov.: 32

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

GnomAD3 exomes AF: 0.00394 AC: 963 AN: 244164 Hom.: 30 AF XY: 0.00299 AC XY: 395 AN XY: 132232

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 SAS exome AF: 0.0000337

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.: 65 Cov.: 30 AF XY: 0.00138 AC XY: 1005 AN XY: 725660

Gnomad4 AFR exome AF: 0.0542

Gnomad4 AMR exome AF: 0.00349

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000151

Gnomad4 SAS exome AF: 0.000164

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000135

Gnomad4 OTH exome AF: 0.00401

GnomAD4 genome AF: 0.0163 AC: 2490 AN: 152322 Hom.: 70 Cov.: 32 AF XY: 0.0160 AC XY: 1189 AN XY: 74488

Gnomad4 AFR AF: 0.0557

Gnomad4 AMR AF: 0.00810

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.00957 Hom.: 11

Bravo AF: 0.0182

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0506 AC: 223

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.00487 AC: 591

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.40
Cadd	Benign	0.086
Dann	Uncertain	0.99
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0029	N
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N
PROVEAN	Benign	0.69	N
REVEL	Benign	0.086
Sift	Benign	0.94	T
Vest4		0.11
MVP		0.12
ClinPred		0.0087	T
GERP RS		-2.8

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: rs17074546; hg19: chr3-42567473;