rs144670843

Variant names:

• chr3-42525971-A-G
• rs144670843
• NM_004624.4:c.377A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_004624.4(VIPR1):​c.377A>G​(p.Asp126Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,613,234 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (32 hom.)
• Consequence: VIPR1 NM_004624.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.07
• Publications: 8 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0042209923).
• BP6: Variant 3-42525971-A-G is Benign according to our data. Variant chr3-42525971-A-G is described in ClinVar as Benign. ClinVar VariationId is 731807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000998 (152/152322) while in subpopulation EAS AF = 0.0211 (109/5166). AF 95% confidence interval is 0.0179. There are 0 homozygotes in GnomAd4. There are 88 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 32 gene

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.377A>G	p.Asp126Gly	missense	Exon 4 of 13	NP_004615.2
	VIPR1	NM_001251885.2		c.296A>G	p.Asp99Gly	missense	Exon 4 of 13	NP_001238814.1	B4DNY6
	VIPR1	NM_001251882.2		c.254A>G	p.Asp85Gly	missense	Exon 5 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.377A>G	p.Asp126Gly	missense	Exon 4 of 13	ENSP00000327246.4	P32241-1
	VIPR1	ENST00000883021.1		c.407A>G	p.Asp136Gly	missense	Exon 4 of 13	ENSP00000553080.1
	VIPR1	ENST00000883016.1		c.377A>G	p.Asp126Gly	missense	Exon 4 of 13	ENSP00000553075.1

Frequencies

GnomAD3 genomes AF: 0.000999 AC: 152 AN: 152204 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000458

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.0211

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.00170 AC: 420 AN: 247650 AF XY: 0.00164

Gnomad AFR exome AF: 0.000315

Gnomad AMR exome AF: 0.0000874

Gnomad ASJ exome AF: 0.00210

Gnomad EAS exome AF: 0.0193

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000893

Gnomad OTH exome AF: 0.000828

GnomAD4 exome AF: 0.00106 AC: 1555 AN: 1460912 Hom.: 32 Cov.: 31 AF XY: 0.00107 AC XY: 775 AN XY: 726592

African (AFR) AF: 0.000179 AC: 6 AN: 33472

American (AMR) AF: 0.000179 AC: 8 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.00161 AC: 42 AN: 26114

East Asian (EAS) AF: 0.0316 AC: 1254 AN: 39682

South Asian (SAS) AF: 0.00130 AC: 112 AN: 85904

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000252 AC: 28 AN: 1111646

Other (OTH) AF: 0.00174 AC: 105 AN: 60366

GnomAD4 genome AF: 0.000998 AC: 152 AN: 152322 Hom.: 0 Cov.: 32 AF XY: 0.00118 AC XY: 88 AN XY: 74484

African (AFR) AF: 0.000457 AC: 19 AN: 41584

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.0211 AC: 109 AN: 5166

South Asian (SAS) AF: 0.00332 AC: 16 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.000997 Hom.: 2

Bravo AF: 0.00108

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00159 AC: 193

Asia WGS AF: 0.0140 AC: 49 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000595

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.65	T
MetaRNN	Benign	0.0042	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.1
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.11
Sift	Benign	0.27	T
Sift4G	Benign	0.31	T
Polyphen		0.33	B
Vest4		0.25
MVP		0.40
MPC		0.13
ClinPred		0.014	T
GERP RS		2.5
Varity_R		0.12
gMVP		0.81
Mutation Taster		=99/1	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: rs144670843; hg19: chr3-42567463;