3-42519271-G-A

Variant names:

• chr3-42519271-G-A
• rs201078991
• NM_004624.4:c.233G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_004624.4(VIPR1):​c.233G>A​(p.Arg78Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,610,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: VIPR1 NM_004624.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00300
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16369715).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VIPR1	NM_004624.4	c.233G>A	p.Arg78Gln	missense_variant	Exon 3 of 13	ENST00000325123.5	NP_004615.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VIPR1	ENST00000325123.5	c.233G>A	p.Arg78Gln	missense_variant	Exon 3 of 13	1	NM_004624.4	ENSP00000327246.4

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152184 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000202 AC: 5 AN: 247496 AF XY: 0.0000149

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000444

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000219 AC: 32 AN: 1458378 Hom.: 0 Cov.: 30 AF XY: 0.0000234 AC XY: 17 AN XY: 725338

African (AFR) AF: 0.00 AC: 0 AN: 33356

American (AMR) AF: 0.00 AC: 0 AN: 44224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39378

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85410

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5760

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1110508

Other (OTH) AF: 0.0000664 AC: 4 AN: 60272

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152184 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74348

African (AFR) AF: 0.0000241 AC: 1 AN: 41466

American (AMR) AF: 0.0000655 AC: 1 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.000110

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 09, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.233G>A (p.R78Q) alteration is located in exon 3 (coding exon 3) of the VIPR1 gene. This alteration results from a G to A substitution at nucleotide position 233, causing the arginine (R) at amino acid position 78 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.75
DEOGEN2	Benign	0.024	.;T;.;.;T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.63	T;T;T;T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.16	T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.3	.;.;.;.;L
PhyloP100		0.0030
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.31	N;N;N;N;N
REVEL	Benign	0.099
Sift	Uncertain	0.019	D;D;D;T;D
Sift4G	Uncertain	0.029	D;T;D;T;D
Polyphen		0.85	.;.;.;.;P
Vest4		0.10
MVP		0.52
MPC		0.10
ClinPred		0.090	T
GERP RS		0.67
Varity_R		0.038
gMVP		0.71
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs201078991; hg19: chr3-42560763;