rs201942399

Variant names:

• chr3-42519304-T-C
• rs201942399
• NM_004624.4:c.266T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_004624.4(VIPR1):​c.266T>C​(p.Ile89Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000882 in 1,609,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000088 (0 hom.)
• Consequence: VIPR1 NM_004624.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.59
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05663219).
• BP6: Variant 3-42519304-T-C is Benign according to our data. Variant chr3-42519304-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 765342.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004624.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VIPR1	NM_004624.4	MANE Select	c.266T>C	p.Ile89Thr	missense	Exon 3 of 13	NP_004615.2
	VIPR1	NM_001251885.2		c.185T>C	p.Ile62Thr	missense	Exon 3 of 13	NP_001238814.1	B4DNY6
	VIPR1	NM_001251882.2		c.143T>C	p.Ile48Thr	missense	Exon 4 of 14	NP_001238811.1	P32241-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VIPR1	ENST00000325123.5	TSL:1 MANE Select	c.266T>C	p.Ile89Thr	missense	Exon 3 of 13	ENSP00000327246.4	P32241-1
	VIPR1	ENST00000883021.1		c.266T>C	p.Ile89Thr	missense	Exon 3 of 13	ENSP00000553080.1
	VIPR1	ENST00000883016.1		c.266T>C	p.Ile89Thr	missense	Exon 3 of 13	ENSP00000553075.1

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152160 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000150 AC: 37 AN: 246836 AF XY: 0.000135

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00250

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000800

Gnomad OTH exome AF: 0.000505

GnomAD4 exome AF: 0.0000885 AC: 129 AN: 1457750 Hom.: 0 Cov.: 30 AF XY: 0.0000869 AC XY: 63 AN XY: 725000

African (AFR) AF: 0.00 AC: 0 AN: 33348

American (AMR) AF: 0.00 AC: 0 AN: 44162

Ashkenazi Jewish (ASJ) AF: 0.00318 AC: 83 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39342

South Asian (SAS) AF: 0.00 AC: 0 AN: 85258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.0000243 AC: 27 AN: 1110174

Other (OTH) AF: 0.000315 AC: 19 AN: 60272

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152160 Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5 AN XY: 74338

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000239 Hom.: 0

Bravo AF: 0.000121

ExAC AF: 0.0000988 AC: 12

EpiCase AF: 0.000111

EpiControl AF: 0.0000602

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.089	T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.21
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.6
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.18
Sift	Benign	0.057	T
Sift4G	Benign	0.10	T
Polyphen		0.89	P
Vest4		0.67
MutPred		0.60		Loss of stability (P = 0.0078)
MVP		0.73
MPC		0.50
ClinPred		0.11	T
GERP RS		3.6
Varity_R		0.10
gMVP		0.72
Mutation Taster		=82/18	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: rs201942399; hg19: chr3-42560796;