3-42513831-C-A

Variant names:

• chr3-42513831-C-A
• rs140984283
• NM_004624.4:c.161C>A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004624.4(VIPR1):​c.161C>A​(p.Ala54Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00243 in 1,551,556 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (6 hom.)
• Consequence: VIPR1 NM_004624.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.722

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005968094).
• BS2: High Homozygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VIPR1	NM_004624.4	c.161C>A	p.Ala54Asp	missense_variant	Exon 2 of 13	ENST00000325123.5	NP_004615.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VIPR1	ENST00000325123.5	c.161C>A	p.Ala54Asp	missense_variant	Exon 2 of 13	1	NM_004624.4	ENSP00000327246.4

Frequencies

GnomAD3 genomes AF: 0.00139 AC: 211 AN: 152150 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00278

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.00118 AC: 185 AN: 156354 Hom.: 1 AF XY: 0.00106 AC XY: 87 AN XY: 82244

Gnomad AFR exome AF: 0.000114

Gnomad AMR exome AF: 0.000121

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000390

Gnomad NFE exome AF: 0.00283

Gnomad OTH exome AF: 0.000908

GnomAD4 exome AF: 0.00254 AC: 3554 AN: 1399288 Hom.: 6 Cov.: 30 AF XY: 0.00236 AC XY: 1629 AN XY: 690184

Gnomad4 AFR exome AF: 0.000190

Gnomad4 AMR exome AF: 0.000168

Gnomad4 ASJ exome AF: 0.0000795

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000252

Gnomad4 FIN exome AF: 0.000609

Gnomad4 NFE exome AF: 0.00315

Gnomad4 OTH exome AF: 0.00185

GnomAD4 genome AF: 0.00139 AC: 211 AN: 152268 Hom.: 1 Cov.: 32 AF XY: 0.00129 AC XY: 96 AN XY: 74442

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00278

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.00244 Hom.: 0

Bravo AF: 0.00153

TwinsUK AF: 0.00324 AC: 12

ALSPAC AF: 0.00259 AC: 10

ESP6500AA AF: 0.000484 AC: 2

ESP6500EA AF: 0.00213 AC: 17

ExAC AF: 0.000624 AC: 42

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 06, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.161C>A (p.A54D) alteration is located in exon 2 (coding exon 2) of the VIPR1 gene. This alteration results from a C to A substitution at nucleotide position 161, causing the alanine (A) at amino acid position 54 to be replaced by an aspartic acid (D). 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	0.12
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.059	.;T;.;T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.45	T;T;T;T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.0060	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	.;.;.;L
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.2	N;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.22	T;T;T;T
Sift4G	Benign	0.63	T;D;D;T
Polyphen		0.54	.;.;.;P
Vest4		0.20
MVP		0.42
MPC		0.13
ClinPred		0.010	T
GERP RS		2.3
Varity_R		0.11
gMVP		0.75

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: rs140984283; hg19: chr3-42555323; COSMIC: COSV57296768; COSMIC: COSV57296768;