Genetic Variant VIPR1:p.Ala75Gly (chr3-42519262-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_004624.4(VIPR1):c.224C>G(p.Ala75Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. A75D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

VIPR1
NM_004624.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.03

Publications

0 publications found

Variant links:

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 links:

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

VIPR1-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26716006).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VIPR1	NM_004624.4	MANE Select	c.224C>G	p.Ala75Gly	missense	Exon 3 of 13	NP_004615.2
VIPR1	NM_001251885.2		c.143C>G	p.Ala48Gly	missense	Exon 3 of 13	NP_001238814.1	B4DNY6
VIPR1	NM_001251882.2		c.101C>G	p.Ala34Gly	missense	Exon 4 of 14	NP_001238811.1	P32241-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VIPR1	ENST00000325123.5	TSL:1 MANE Select	c.224C>G	p.Ala75Gly	missense	Exon 3 of 13	ENSP00000327246.4	P32241-1
VIPR1	ENST00000883021.1		c.224C>G	p.Ala75Gly	missense	Exon 3 of 13	ENSP00000553080.1
VIPR1	ENST00000883016.1		c.224C>G	p.Ala75Gly	missense	Exon 3 of 13	ENSP00000553075.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458284

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725284

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33346

American (AMR)

AF:

0.00

AC:

AN:

44228

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26070

East Asian (EAS)

AF:

0.00

AC:

AN:

39392

South Asian (SAS)

AF:

0.00

AC:

AN:

85362

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1110452

Other (OTH)

AF:

0.00

AC:

AN:

60288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.042

Eigen

Benign

0.077

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.30

M_CAP

Benign

0.013

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.87

MutationAssessor

Benign

2.0

PhyloP100

2.0

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.4

REVEL

Benign

0.038

Sift

Uncertain

0.011

Sift4G

Benign

0.20

Polyphen

0.44

Vest4

0.28

MutPred

0.37

Gain of glycosylation at T76 (P = 0.0677)

MVP

0.68

MPC

0.28

ClinPred

0.56

GERP RS

3.5

Varity_R

0.14

gMVP

0.56

Mutation Taster

=79/21

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over