3-42519271-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004624.4(VIPR1):​c.233G>T​(p.Arg78Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R78Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: VIPR1 NM_004624.4 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08957034).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VIPR1	NM_004624.4	c.233G>T	p.Arg78Leu	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>T	p.Arg78Leu	missense_variant	Exon 3 of 13	1	NM_004624.4	ENSP00000327246.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	11
DANN	Benign	0.81
DEOGEN2	Benign	0.016	.;T;.;.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.62	T;T;T;T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.090	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.075	.;.;.;.;N
PhyloP100		0.0030
PrimateAI	Benign	0.42	T
PROVEAN	Benign	2.8	N;N;N;N;N
REVEL	Benign	0.059
Sift	Benign	0.29	T;T;T;T;T
Sift4G	Benign	0.21	T;T;T;T;T
Polyphen		0.0010	.;.;.;.;B
Vest4		0.065
MutPred		0.55		.;.;.;Loss of solvent accessibility (P = 0.0606);Loss of solvent accessibility (P = 0.0606);
MVP		0.30
MPC		0.11
ClinPred		0.15	T
GERP RS		0.67
Varity_R		0.046
gMVP		0.78
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; COSMIC: COSV100285714; COSMIC: COSV100285714;