3-42528101-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004624.4(VIPR1):c.614C>T(p.Ser205Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00419 in 1,613,826 control chromosomes in the GnomAD database, including 230 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (134 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (96 hom.)
• Consequence: VIPR1 NM_004624.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.05

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022152364).
• BP6: Variant 3-42528101-C-T is Benign according to our data. Variant chr3-42528101-C-T is described in ClinVar as [Benign]. Clinvar id is 767897.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VIPR1	NM_004624.4	c.614C>T	p.Ser205Leu	missense_variant	6/13	ENST00000325123.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VIPR1	ENST00000325123.5	c.614C>T	p.Ser205Leu	missense_variant	6/13	1	NM_004624.4	P4
VIPR1-AS1	ENST00000452639.7	n.952+448G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0213 AC: 3235 AN: 152152 Hom.: 133 Cov.: 32

Gnomad AFR AF: 0.0743

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00648

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0139

GnomAD3 exomes AF: 0.00576 AC: 1447 AN: 251148 Hom.: 35 AF XY: 0.00421 AC XY: 572 AN XY: 135722

Gnomad AFR exome AF: 0.0764

Gnomad AMR exome AF: 0.00394

Gnomad ASJ exome AF: 0.0000995

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000396

Gnomad OTH exome AF: 0.00327

GnomAD4 exome AF: 0.00240 AC: 3512 AN: 1461556 Hom.: 96 Cov.: 31 AF XY: 0.00207 AC XY: 1504 AN XY: 727112

Gnomad4 AFR exome AF: 0.0783

Gnomad4 AMR exome AF: 0.00450

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000232

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.000258

Gnomad4 OTH exome AF: 0.00561

GnomAD4 genome AF: 0.0214 AC: 3255 AN: 152270 Hom.: 134 Cov.: 32 AF XY: 0.0204 AC XY: 1522 AN XY: 74442

Gnomad4 AFR AF: 0.0746

Gnomad4 AMR AF: 0.00647

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.00247 Hom.: 13

Bravo AF: 0.0248

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0747 AC: 329

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.00689 AC: 836

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000237

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

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.76
Cadd	Benign	0.49
Dann	Benign	0.85
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.20	T;T;T
MetaRNN	Benign	0.0022	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Benign	0.023
Sift	Benign	0.55	T;T;T
Sift4G	Benign	0.54	T;T;T
Polyphen		0.0010	.;.;B
Vest4		0.22
MVP		0.14
MPC		0.077
ClinPred		0.00072	T
GERP RS		-5.3
Varity_R		0.045
gMVP		0.22

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: rs115435479; hg19: chr3-42569593; COSMIC: COSV57297726; COSMIC: COSV57297726;